The International Symposium on

Development and PLASTICITYofNEURAL SYSTEMSFor speakers in Japan & Asia
The International Symposium on Development and Plasticity of Neural Systems* The time shown below is JST/Japan Standard Time
Tuesday, 15 March(Day 2)

9:00

S-7 Zhigang He

Short oral talk (P-1 ~ P-15)
Talk time: 10-min/person
Break: 20-min

9:30
9:50

S-8 Yutaka Yoshida(Burke Neurological Institute/Weill
Cornell Medicine/OIST)S-9 Tadashi Isa(Kyoto University)

10:10
10:30

Break
S-10 Hideyuki Okano(RIKEN CBS/Keio University)

10:50

S-11 Mark H. Tuszynski(University of California,
San Diego)

11:20

S-12 Jun Takahashi(Kyoto University)

11:40

Opening: Tadashi Isa

S-3 Haruo Kasai(The University of Tokyo)

18:20
18:40

Break
S-4 Michisuke Yuzaki(Keio University)

19:00

S-5 Ole Kiehn(University of Copenhagen/
Karolinska Institute)

19:30

S-13 Adrian W Moore(Institute of Neuroscience,
CSIC-UMH)

18:10
18:30

Break
S-16 Carina Hanashima(Waseda University)

18:50 S-17 Chiaki Ohtaka-Maruyama(TMIMS)

19:10

S-18 Jonas Frisén(Karolinska Institute)
S-6 Martin E. Schwab(University of Zurich)

10:20
10:40

19:40

20:00

11:00

9:50

S-32 Haruhiko Bito

(The University of Tokyo)

10:10
10:30

Break
S-33 Hitoshi Okamoto(RIKEN CBS)

10:50

S-34 Yoko Yazaki-Sugiyama(OIST/The University of Tokyo)
S-35 Takeshi Imai

11:30

P-7 Tadao Usui

11:30

P-13 Kosuke Hamaguchi

12:00

P-9 Ayano Kawaguchi

12:00

P-15 Pin-Wu Liu

17:00

S-24 Itaru Imayoshi

17:00

S-36 Kazunori Nakajima

17:20

S-25 Fumio Matsuzaki(RIKEN BDR)

17:40

S-26 Jürgen A Knoblich(IMBA/Medical University of
Vienna)

18:10

Break

18:30
S-27 Pierre Vanderhaeghen(VIB-KU Leuven)

19:00

S-28 J. Gray Camp

(Roche Institute for Translational
Bioengineering)

19:30

S-29 Mototsugu Eiraku

19:50

P-10 Goichi Miyoshi(Kyoto University)
P-11 Sara Morson
P-12 Masaaki Ogawa

20:20

20:40

Networking
20:50

21:00

S-23 Arnold Kriegstein(Stanford University)

11:10

P-6 Masafumi Inaba

Networking

S-31 Karl Deisseroth(University of California,
San Francisco)

20:10
Networking

S-22 Kazunobu Sawamoto(Nagoya City University/National
Institute for Physiological Sciences)

P-4 Yoshitaka Kameo
P-5 Tomoki Matsuda

Break(Kyoto University)

S-14 Mineko Kengaku

S-15 Victor Borrell

S-21 Freda Miller(University of British Columbia)(Kyoto University)

17:40(RIKEN CBS)

(Kyushu University)

P-8 Haruka Sato

Session 5 (Chair: Kazunori Nakajima)

18:00

17:00
17:20

S-2 Mu-ming Poo(Institute of Neuroscience, Chinese
Academy of Sciences)

9:50

S-30 Masanori Murayama

9:20

S-20 Yukiko Gotoh(The University of Tokyo)(RIKEN CBS)

(Kyoto University)

17:30

P-3 Yusuke Kishi

S-1 Yasunori Hayashi

Session 3 (Chair: Mototsugu Eiraku)

Session 1
Part2 (Chair: Yasunori Hayashi) Part1 (Chair: Tadashi Isa)

17:00
17:10

9:30

P-1 Yuki Fujita
P-2 Miaoxing Wang

12:10

9:00

S-19 Hongjun Song

(University of Pennsylvania)

Session 4 (Chair: Ryoichiro Kageyama)

Invited Speakers (S-1 ~ S-39)
Talk time
International: 30-min/person
Japanese and Japanese resident:
20-min/person

Session 2 (Chair: Yoko Yazaki-Sugiyama)(Harvard Medical School)

Thursday, 17 March(Day 4)

Session 6 (Chair: Tadashi Isa)

9:00

Wednesday, 16 March(Day 3)

P-14 Rikako Kato

Session 7 (Chair: Yukiko Gotoh)

Monday, 14 March(Day 1)(Keio Univeristy)

17:20

S-37 Sebastian Jessberger(University of Zurich)

17:50

S-38 Magdalena Götz

(University of Munich)

18:20

S-39 Ryoichiro Kageyama(RIKEN CBS/Kyoto University)

18:40

Closing: Magdalena Götz

For speakers in Europe
The International Symposium on Development and Plasticity of Neural Systems* The time shown below is CET/Central European Time
Tuesday, 15 March(Day 2)

1:00

S-7 Zhigang He

Short oral talk (P-1 ~ P-15)
Talk time: 10-min/person
Break: 20-min

1:30
1:50

S-8 Yutaka Yoshida(Burke Neurological Institute/Weill
Cornell Medicine/OIST)S-9 Tadashi Isa(Kyoto University)

2:10
2:30

Break
S-10 Hideyuki Okano(RIKEN CBS/Keio University)

2:50

S-11 Mark H. Tuszynski(University of California,
San Diego)

3:20

S-12 Jun Takahashi(Kyoto University)

3:40

Opening: Tadashi Isa

S-3 Haruo Kasai(The University of Tokyo)

10:20
10:40

Break
S-4 Michisuke Yuzaki(Keio University)

11:00

S-5 Ole Kiehn(University of Copenhagen/
Karolinska Institute)

11:30

S-13 Adrian W Moore(Institute of Neuroscience,
CSIC-UMH)

10:10
10:30

Break
S-16 Carina Hanashima(Waseda University)

10:50 S-17 Chiaki Ohtaka-Maruyama(TMIMS)

11:10

S-18 Jonas Frisén(Karolinska Institute)
S-6 Martin E. Schwab(University of Zurich)

2:20
2:40

11:40

12:00

3:00

1:50

S-32 Haruhiko Bito

(The University of Tokyo)

2:10
2:30

Break
S-33 Hitoshi Okamoto(RIKEN CBS)

2:50

S-34 Yoko Yazaki-Sugiyama(OIST/The University of Tokyo)
S-35 Takeshi Imai

3:30

P-7 Tadao Usui

3:30

P-13 Kosuke Hamaguchi

4:00

P-9 Ayano Kawaguchi

4:00

P-15 Pin-Wu Liu

9:00

S-24 Itaru Imayoshi

9:00

S-36 Kazunori Nakajima

9:20

S-25 Fumio Matsuzaki(RIKEN BDR)

9:40

S-26 Jürgen A Knoblich(IMBA/Medical University of
Vienna)

10:10

Break

10:30
S-27 Pierre Vanderhaeghen(VIB-KU Leuven)

11:00

S-28 J. Gray Camp

(Roche Institute for Translational
Bioengineering)

11:30

S-29 Mototsugu Eiraku

11:50

P-10 Goichi Miyoshi(Kyoto University)
P-11 Sara Morson
P-12 Masaaki Ogawa

12:20

12:40

Networking
12:50

13:00

S-23 Arnold Kriegstein(Stanford University)

3:10

P-6 Masafumi Inaba

Networking

S-31 Karl Deisseroth(University of California,
San Francisco)

12:10
Networking

S-22 Kazunobu Sawamoto(Nagoya City University/National
Institute for Physiological Sciences)

P-4 Yoshitaka Kameo
P-5 Tomoki Matsuda

Break(Kyoto University)

S-14 Mineko Kengaku

S-15 Victor Borrell

S-21 Freda Miller(University of British Columbia)(Kyoto University)

9:40(RIKEN CBS)

(Kyushu University)

P-8 Haruka Sato

Session 5 (Chair: Kazunori Nakajima)

10:00

9:00
9:20

S-2 Mu-ming Poo(Institute of Neuroscience, Chinese
Academy of Sciences)

1:50

S-30 Masanori Murayama

1:20

S-20 Yukiko Gotoh(The University of Tokyo)(RIKEN CBS)

(Kyoto University)

9:30

P-3 Yusuke Kishi

S-1 Yasunori Hayashi

Session 3 (Chair: Mototsugu Eiraku)

Session 1
Part2 (Chair: Yasunori Hayashi) Part1 (Chair: Tadashi Isa)

9:00
9:10

1:30

P-1 Yuki Fujita
P-2 Miaoxing Wang

4:10

1:00

S-19 Hongjun Song

(University of Pennsylvania)

Session 4 (Chair: Ryoichiro Kageyama)

Invited Speakers (S-1 ~ S-39)
Talk time
International: 30-min/person
Japanese and Japanese resident:
20-min/person

Session 2 (Chair: Yoko Yazaki-Sugiyama)(Harvard Medical School)

Thursday, 17 March(Day 4)

Session 6 (Chair: Tadashi Isa)

1:00

Wednesday, 16 March(Day 3)

P-14 Rikako Kato

Session 7 (Chair: Yukiko Gotoh)

Monday, 14 March(Day 1)(Keio Univeristy)

9:20

S-37 Sebastian Jessberger(University of Zurich)

9:50

S-38 Magdalena Götz

(University of Munich)

10:20

S-39 Ryoichiro Kageyama(RIKEN CBS/Kyoto University)

10:40

Closing: Magdalena Götz

For speakers in US East
The International Symposium on Development and Plasticity of Neural Systems* The time shown below is EDT /Eastern Daylight Time (US East)

4:00(Kyoto University)

S-3 Haruo Kasai(The University of Tokyo)

5:20
5:40

Break
S-4 Michisuke Yuzaki(Keio University)

6:00

S-5 Ole Kiehn(University of Copenhagen/
Karolinska Institute)

6:30
S-6 Martin E. Schwab

4:40

4:20

S-14 Mineko Kengaku(Institute of Neuroscience,
CSIC-UMH)

5:10
5:30

Break
S-16 Carina Hanashima(Waseda University)

5:50 S-17 Chiaki Ohtaka-Maruyama(TMIMS)

6:10

S-18 Jonas Frisén(Karolinska Institute)

6:40(University of Zurich)

S-15 Victor Borrell

S-25 Fumio Matsuzaki(RIKEN BDR)

4:40

S-26 Jürgen A Knoblich(IMBA/Medical University of
Vienna)

5:10
5:30

Break
S-27 Pierre Vanderhaeghen(VIB-KU Leuven)

6:00

4:00

S-36 Kazunori Nakajima(Keio Univeristy)

4:20

S-37 Sebastian Jessberger(University of Zurich)

4:50

S-38 Magdalena Götz

(University of Munich)

5:20

S-39 Ryoichiro Kageyama(RIKEN CBS/Kyoto University)

5:40

Closing: Magdalena Götz

S-28 J. Gray Camp

(Roche Institute for Translational
Bioengineering)

6:30

S-29 Mototsugu Eiraku(Kyoto University)

P-4 Yoshitaka Kameo
P-5 Tomoki Matsuda

6:50

P-6 Masafumi Inaba

P-10 Goichi Miyoshi
P-11 Sara Morson

7:10

P-12 Masaaki Ogawa

Networking

Networking

S-24 Itaru Imayoshi(Kyoto University)(Kyoto University)

S-2 Mu-ming Poo(Institute of Neuroscience, Chinese
Academy of Sciences)

5:00

4:20
Session 3 (Chair: Mototsugu Eiraku)

4:30

4:00

S-13 Adrian W Moore(RIKEN CBS)S-1 Yasunori Hayashi

Thursday, 17 March

Session 7 (Chair : Yukiko Gotoh )Opening: Tadashi Isa

Wednesday, 16 March

Session 5 (Chair: Kazunori Nakajima)

4:00
4:10

Tuesday, 15 March

7:00

7:20

7:40

Networking
7:50

8:00

20:00

20:00

S-7 Zhigang He(Harvard Medical School)

20:00

S-19 Hongjun Song

S-30 Masanori Murayama(RIKEN CBS)

(University of Pennsylvania)

20:50

S-8 Yutaka Yoshida(Burke Neurological Institute/Weill
Cornell Medicine/OIST)S-9 Tadashi Isa(Kyoto University)

21:10
21:30

Break
S-10 Hideyuki Okano(RIKEN CBS/Keio University)

21:50

S-11 Mark H. Tuszynski(University of California,
San Diego)

22:20

P-3 Yusuke Kishi

S-21 Freda Miller(University of British Columbia)

21:20
21:40

Break
S-22 Kazunobu Sawamoto(Nagoya City University/National
Institute for Physiological Sciences)

22:00

S-23 Arnold Kriegstein(Stanford University)

20:50

S-32 Haruhiko Bito

(The University of Tokyo)

21:10
21:30

Break
S-33 Hitoshi Okamoto(RIKEN CBS)

21:50

S-34 Yoko Yazaki-Sugiyama(OIST/The University of Tokyo)(University of California,
San Francisco)

22:10

S-35 Takeshi Imai

22:30

P-7 Tadao Usui

22:30

P-13 Kosuke Hamaguchi

23:00

P-9 Ayano Kawaguchi

P-1 Yuki Fujita
P-2 Miaoxing Wang

23:10

20:50

S-31 Karl Deisseroth

S-20 Yukiko Gotoh(The University of Tokyo)

S-12 Jun Takahashi(Kyoto University)

22:40

20:30

Session 6 (Chair: Tadashi Isa)

20:30

Session 4 (Chair: Ryoichiro Kageyama)

20:20
Session 2 (Chair: Yoko Yazaki-Sugiyama)

Session 1

Part2 (Chair: Yasunori Hayashi) Part1 (Chair: Tadashi Isa)

Monday, 14 March(Kyushu University)

P-8 Haruka SatoP-14 Rikako Kato

23:00

P-15 Pin-Wu Liu

Invited Speakers (S-1 ~ S-39)
Talk time
International: 30-min/person
Japanese and Japanese resident:
20-min/person
Short oral talk (P-1 ~ P-15)
Talk time: 10-min/person
Break: 20-min

For speakers in US WestThe International Symposium on Development and Plasticity of Neural Systems* The time shown below is PDT Pacific Daylight Time (US West)

1:00

S-3 Haruo Kasai(The University of Tokyo)

2:20
2:40

Break
S-4 Michisuke Yuzaki(Keio University)

3:00

S-5 Ole Kiehn(University of Copenhagen/
Karolinska Institute)

1:20

S-14 Mineko Kengaku(Kyoto University)

1:40(Institute of Neuroscience,
CSIC-UMH)

2:10
2:30

S-16 Carina Hanashima(Waseda University)(TMIMS)

3:10

S-18 Jonas Frisén(Karolinska Institute)

3:40(University of Zurich)Break2:50 S-17 Chiaki Ohtaka-Maruyama

3:30
S-6 Martin E. Schwab

S-15 Victor Borrell

S-25 Fumio Matsuzaki(RIKEN BDR)

1:40

S-26 Jürgen A Knoblich(IMBA/Medical University of
Vienna)

2:10

Break

2:30
S-27 Pierre Vanderhaeghen(VIB-KU Leuven)

3:00

Thursday, 17 March
1:00

S-36 Kazunori Nakajima(Keio Univeristy)

1:20

S-37 Sebastian Jessberger(University of Zurich)

1:50

S-38 Magdalena Götz

(University of Munich)

2:20

S-39 Ryoichiro Kageyama(RIKEN CBS/Kyoto University)

2:40

Closing: Magdalena Götz

S-28 J. Gray Camp

(Roche Institute for Translational
Bioengineering)

3:30

S-29 Mototsugu Eiraku

3:50

P-10 Goichi Miyoshi(Kyoto University)

P-4 Yoshitaka Kameo
P-5 Tomoki Matsuda
P-6 Masafumi Inaba

P-11 Sara Morson

4:10

P-12 Masaaki Ogawa

Networking

Networking

S-24 Itaru Imayoshi(Kyoto University)

Session 5 (Chair: Kazunori Nakajima)

2:00

1:20

S-2 Mu-ming Poo(Institute of Neuroscience, Chinese
Academy of Sciences)

1:00

S-13 Adrian W Moore(RIKEN CBS)

(Kyoto University)

1:30

Wednesday, 16 March

Session 7 (Chair : Yukiko Gotoh )Opening: Tadashi Isa
S-1 Yasunori Hayashi

Session 3 (Chair: Mototsugu Eiraku)

Part1 (Chair: Tadashi Isa)
Part2 (Chair: Yasunori Hayashi)

1:00
1:10

Tuesday, 15 March

4:00

4:20

4:40

Networking
4:50

5:00

17:00

17:00

S-7 Zhigang He(Harvard Medical School)

17:00

S-19 Hongjun Song

S-30 Masanori Murayama(RIKEN CBS)

(University of Pennsylvania)

17:50

S-8 Yutaka Yoshida(Burke Neurological Institute/Weill
Cornell Medicine/OIST)S-9 Tadashi Isa(Kyoto University)

18:10
18:30

Break
S-10 Hideyuki Okano(RIKEN CBS/Keio University)

18:50

S-11 Mark H. Tuszynski(University of California,
San Diego)

19:20

20:10

17:50

P-3 Yusuke Kishi

S-21 Freda Miller(University of British Columbia)

18:20
18:40

Break
S-22 Kazunobu Sawamoto(Nagoya City University/National
Institute for Physiological Sciences)

19:00(Stanford University)

S-23 Arnold Kriegstein

17:50

S-32 Haruhiko Bito

(The University of Tokyo)

18:10
18:30

Break
S-33 Hitoshi Okamoto(RIKEN CBS)

18:50

S-34 Yoko Yazaki-Sugiyama(OIST/The University of Tokyo)(University of California,
San Francisco)

19:10

S-35 Takeshi Imai

19:30

P-7 Tadao Usui

19:30

P-13 Kosuke Hamaguchi

20:00

P-9 Ayano Kawaguchi

P-1 Yuki Fujita
P-2 Miaoxing Wang

S-31 Karl Deisseroth

S-20 Yukiko Gotoh(The University of Tokyo)

S-12 Jun Takahashi(Kyoto University)

19:40

17:30

Session 6 (Chair: Tadashi Isa)

17:30

Session 4 (Chair: Ryoichiro Kageyama)

17:20
Session 2 (Chair: Yoko Yazaki-Sugiyama)

Session 1

Monday, 14 March(Kyushu University)

P-8 Haruka SatoP-14 Rikako Kato

20:00

P-15 Pin-Wu Liu

Invited Speakers (S-1 ~ S-39)
Talk time
International: 30-min/person
Japanese and Japanese resident:
20-min/person
Short oral talk (P-1 ~ P-15)
Talk time: 10-min/person
Break: 20-min

Monday, March 14 (Day 1)
Opening Remarks
17:00-17:10

Tadashi Isa

Chair: Tadashi Isa
17:10-17:30 S-1 Synaptic plasticity during sleep is required for memory
Yasunori Hayashi (Kyoto University)
17:30-18:00 S-2 Dynamics and stability of synaptic connections in adult mice and monkey brain
Mu-ming Poo (Institute of Neuroscience, Chinese Academy of Sciences)
18:00-18:20 S-3 The force of dendritic-spine enlargement facilitating presynaptic exocytosis
Haruo Kasai (The University of Tokyo)
18:20-18:40

Break

Chair: Yasunori Hayashi
18:40-19:00 S-4 Bridge over Troubled Synapses with Extracellular Scaffolding Proteins
Michisuke Yuzaki (Keio University)
19:00-19:30 S-5 Brainstem circuits controlling arrest of movements
Ole Kiehn (University of Copenhagen/Karolinska Institute)
From the bench to clinical trials for regeneration enhancing Nogo-A antibodies for
19:30-20:00 S-6
spinal cord injury
Martin E. Schwab (University of Zurich)
20:00-21:00

Networking

Tuesday, March 15 (Day 2 - Morning)
Chair: Yoko Yazaki-Sugiyama
9:00-9:30

S-7 How do injured CNS neurons respond to axonal insults?
Zhigang He (Harvard Medical School)

9:30-9:50

9:50-10:10

Monosynaptic connections between corticospinal neurons and motor neurons
underlying manual dexterity in wild-type and ALS model mice
Yutaka Yoshida (Burke Neurological Institute/Weill Cornell Medicine,
Okinawa Institute of Science and Technology graduate University)
S-9 How the brain works for recovery from spinal cord injury
S-8

Tadashi Isa (Kyoto University)
10:10-10:30

Break

10:30-10:50 S-10

Disease Modeling using Marmosets with Germ Line Modification and In Vivo
Genome Editing
Hideyuki Okano (RIKEN CBS/Keio University)

10:50-11:20 S-11 Rhesus Macaque vs Rat Divergence in the Corticospinal ProjectomeMark H. Tuszynski (University of California, San Diego)
11:20-11:40 S-12 iPS cell-based therapy for Parkinson’s disease
Jun Takahashi (Kyoto University)
11:40-12:10

Short Oral Talks (P-1 ~ P-3)

11:40-11:50 P-1 Yuki Fujita (University of Pennsylvania)
11:50-12:00 P-2 Miaoxing Wang (Kanazawa University)
12:00-12:10 P-3 Yusuke Kishi (The University of Tokyo)

Tuesday, March 15 (Day 2 - Evening)
Chair: Mototsugu Eiraku
17:00-17:20 S-13 Genetic strategies to create stereotyped arbor wiring
Adrian W Moore (RIKEN CBS)
17:20-17:40 S-14 Cytoskeletal forces driving neuronal migration in 3D brain tissues
Mineko Kengaku (Kyoto University)
17:40-18:10 S-15 New (and small) regulators of cerebral cortex size and folding during evolution
Victor Borrell (Institute of Neuroscience Alicante)
18:10-18:30

Break

18:30-18:50 S-16 Mechanisms of neuronal subtype transition and integration in the cerebral cortex
Carina Hanashima (Waseda University)
Characteristics of subplate neuron molecular expression elucidated by single-cell
18:50-19:10 S-17
and spatial transcriptome analysis
Chiaki Ohtaka-Maruyama (Tokyo Metropolitan Institute of Medical Science)
19:10-19:40 S-18 Neurogenesis in the adult human hippocampus
Jonas Frisén (Karolinska Institute)
19:40–20:10

Short Oral Talks (P-4 ~ P-6)

19:40-19:50 P-4 Yoshitaka Kameo (Kyoto University)
19:50-20:00 P-5 Tomoki Matsuda (SANKEN, Osaka University)
20:00-20:10 P-6 Masafumi Inaba (Kyoto University)

20:10-20:40

Networking

Wednesday, March 16 (Day 3 - Morning)
Chair: Ryoichiro Kageyama
9:00-9:30

S-19 Neurogenesis in the dentate gyrus of the hippocampus as a continuous evelopmental
process across the lifespanHongjun Song (University of Pennsylvania)

9:30-9:50

S-20 Cell cycle arrest determines adult neural stem cell ontogeny
Yukiko Gotoh (The University of Tokyo)

9:50-10:20 S-21 Defining mammalian neural stem cell transitions and niches from embryogenesis
to adulthood
Freda Miller (University of British Columbia)
10:20-10:40

Break

10:40-11:00 S-22 Postnatal neuronal migration in health and disease
Kazunobu Sawamoto (Nagoya City University/National Institute for Physiological
Sciences)
11:00-11:30 S-23 Genomic Insights into Early Human Brain Development, Evolution, and Disease
Arnold Kriegstein (University of California, San Francisco)
11:30–12:00

Short Oral Talks (P-7 ~ P-9)

11:30-11:40 P-7 Tadao Usui (Kyoto University)
11:40-11:50 P-8 Haruka Sato (Kumamoto University)
11:50-12:00 P-9 Ayano Kawaguchi (Nagoya University)

Wednesday, March 16 (Day 3 - Evening)
Chair: Kazunori Nakajima
17:00-17:20 S-24 Analysis of neural stem cell regulatory mechanisms using optogenetics
Itaru Imayoshi (Kyoto University)
17:20-17:40 S-25

Exploring the relationship of progenitor subtypes in and between gyrencephalicspecies at the single cell level

Fumio Matsuzaki (RIKEN BDR)
A cerebral organoid model for Tuberous sclerosis identifies human-specific aspects
17:40-18:10 S-26
of brain
Jürgen A Knoblich (IMBA/Medical University of Vienna)
18:10-18:30

Break

18:30-19:00 S-27 Human-specific temporal mechanisms of brain development
Pierre Vanderhaeghen (VIB-KU Leuven)
19:00-19:30 S-28 Lineage recording in human cerebral organoids
J. Gray Camp (Roche Institute for Translational Bioengineering)
19:30-19:50 S-29 Neural Development in Stem Cell Culture
Mototsugu Eiraku (Kyoto University)
19:50–20:20

Short Oral Talks (P-10 ~ P-12)

19:50-20:00 P-10 Goichi Miyoshi (Gunma University)
20:00-20:10 P-11 Sarah Morson (Okinawa Institute of Science and Technology Graduate University)
20:10-20:20 P-12 Masaaki Ogawa (Kyoto University)

20:20-20:50

Networking

Thursday, March 17 (Day 4 - Morning)
Chair: Tadashi Isa
9:00-9:20

S-30

Emotional arousal enhances perceptual memory through amygdalo-cortical input
during NREM sleep
Masanori Murayama (RIKEN CBS)

9:20-9:50

S-31 TBA
Karl Deisseroth (Stanford University)

9:50-10:10 S-32 TBA
Haruhiko Bito (The Univresity of Tokyo)
10:10-10:30

Break

10:30-10:50 S-33

Discovery of neurons monitoring whether the prediction comes true in the brain ofzebrafish escaping in the virtual reality space

Hitoshi Okamoto (RIKEN CBS)
Variable axon connectivity of song memory ensembles in developmental zebra finch
10:50-11:10 S-34
song learning
Yoko Yazaki-Sugiyama (OIST/The University of Tokyo)
11:10-11:30 S-35 Lateral inhibition signals for synaptic competitions
Takeshi Imai (Kyushu University)
11:30–12:00

Short Oral Talks (P-13 ~ P-15)

11:30-11:40 P-13 Kosuke Hamaguchi (Kyoto University)
11:40-11:50 P-14 Rikako Kato (Kyoto University)
11:50-12:00 P-15 Pin-Wu Liu (Nagoya University)

Thursday, March 17 (Day 4 - Evening)
Chair: Yukiko Gotoh
17:00-17:20 S-36 Control of astrocyte dispersion in the developing cerebral cortex
Kazunori Nakajima (Keio Univeristy)
17:20-17:50 S-37 Molecular and functional heterogeneity of neural stem cells
Sebastian Jessberger (University of Zurich)
17:50-18:20 S-38

Novel mechanisms of neurogenesis – the centrosome as a dynamic RNA processing
hub in neurogenesis
Magdalena Götz (University of Munich)

18:20-18:40 S-39

Functional rejuvenation of aged neural stem cells by Plagl2 and anti-Dyrk1a
activity
Ryoichiro Kageyama (RIKEN CBS/Kyoto University)

Closing Remarks

18:40-18:50

Magdalena Götz

Short Oral Talks
P-1

Spatial genome organization during neurogenesis
Yuki Fujita (University of Pennsylvania)

P-2

Intracellular trafficking of Notch orchestrates temporal dynamics of Notch activity inthe fly brain
Miaoxing Wang (Kanazawa University)

P-3

The role of PcG in regionalization of the mouse telencephalon
Yusuke Kishi (The University of Tokyo)

P-4

Mechanical modeling of brain morphogenesis caused by multicellular dynamics
Yoshitaka Kameo (Kyoto University)

P-5

Development of fluorescent indicators for visualization of N-cadherin interaction
across cells
Tomoki Matsuda (SANKEN, Osaka University)

P-6

Contractile oscillators regulate the spatial patterning of gut motility
Masafumi Inaba (Kyoto University)

P-7

Elucidation of the internal state-dependent modulation of the nociceptive escapebehavior
Tadao Usui (Kyoto University)

P-8

Thalamocortical axons control the cytoarchitecture of neocortical layers by areaspecific supply of VGFHaruka Sato (Kumamoto University)

P-9

Neuronal delamination and outer radial glia generation in neocortical development
Ayano Kawaguchi (Nagoya University)

P-10

A FOXG1-dependent critical period for autism-associated GABAergic circuits
Goichi Miyoshi (Gunma University)

P-11

Parallel anatomical connections for song memories between two regions of the zebra
finch higher auditory cortex
Sarah Morson (Okinawa Institute of Science and Technology Graduate University)

P-12

The neural basis for overcoming failure: a dopamine circuit facilitates switching toward
new goals
Masaaki Ogawa (Kyoto University)

P-13

From Retrospective to Prospective: Integrated Value Representation in Frontal Cortex
for Predictive Choice Behavior
Kosuke Hamaguchi (Kyoto University)

P-14

Visual instrumental learning without primary visual cortex
Rikako Kato (Kyoto University)

P-15

Regulation of synaptic nanodomain and nanocolumn by liquid–liquid phase separation
Pin-Wu Liu (Nagoya University)

International Symposium on Development and Plasticity of Neural System

S-1
Synaptic plasticity during sleep is required for memory
Yasunori Hayashi
Kyoto University Graduate School of Medicine

Memories are initially formed in the hippocampus but subsequently transferred to the rest of brain fora long-term storage. This phenomenon is called "memory consolidation," but the cellular mechanism
responsible for it has not been fully elucidated. Long-term potentiation (LTP) of synaptictransmission, which increases the efficiency of the transmission of neural activity between cells forlong-term, is known as a cellular phenomenon of memory. If we can determine when and where LTP
occurs, we can dissect out the cellular process responsible for the memory consolidation. We firstdeveloped a technique to detect when and where LTP is occurring. We employed SuperNova, afluorescent protein derived from sea anemones to accomplish this. Upon illumination, SuperNova
releases reactive oxygen species (ROS), which then inactivates the surrounding proteins. We
connected SuperNova with cofilin, an actin binding protein specifically accumulates at the synapse
after LTP induction. Illumination of cofilin-SuperNova caused an erasure of LTP only within 20 min
after the induction. We found light irradiation into the hippocampus immediately after learning or
during sleep after learning leads to erasure of the memories in both cases. This indicates that two
waves of LTP occurred in the hippocampus immediately after learning and during sleep afterwards,
and that these stepwise LTP events shape memories in the hippocampus. To further understand thetime window in which memories are transferred to the cortex, we examined the time window of LTP
in the anterior cingulate cortex, a cortical region implicated in the recall of old memory and found that
LTP was induced in the anterior cingulate cortex during sleep the day after learning but not on thesame day. This technology has the potential to elucidate many brain functions involved in memory at
the cellular level.

International Symposium on Development and Plasticity of Neural System

S-2
Dynamics and stability of synaptic connections in adult mice and monkey brain
Mu-ming Poo. Yang Yang, and Min Chen
Institute of Neuroscience, Chinese Academy of Sciences
Shanghai Center for Brain Research Brain-inspired Technology.

Formation and elimination of synapses reflects structural plasticity of neuronal connectivity. We have
performed in vivo high-resolution two-photon imaging to examine the dynamic turnover of synaptic
structures (dendritic spines and presynaptic boutons) in the primary auditory cortex (A1) of adult miceand the prefrontal cortex (PFC) of adult macaque monkeys. In mice A1, we found that the rate ofturnover of synaptic structures was relatively low (5-10% over two days). By dual-color labeling ofboth axon projections from lateral amygdala and A1 layer 5 pyramidal neurons, we found surprisinglythat essentially all new synapses formed either spontaneously or induced by auditory fear
conditioning involved additions of a presynaptic bouton or a postsynaptic spine to a pre-existing
synapse. This indicates that structural modification of adult mouse brain involves changing thestrength of existing connections, rather than de novo formation of new connections. At the dendritesof layer 5 pyramidal neurons of PFC in four macaque monkeys of different ages, we found that spines
were in general highly stable, with a much lower rate of formation and elimination of synapses thanthose found in the mouse brain. By following the same spines at weekly intervals over months, wefound that newly formed spines in the monkey PFC were more susceptible to elimination, with only
40% surviving long term. Enabled by high-resolution imaging of a large number of spines in themacaque PFC, we performed in-depth analysis of spatial distribution of spines on individual
dendrites, and found that the distances between adjacent spines conform to Weibull distribution, andspine formation and elimination was more likely to occur in low- and high-density regions,
respectively, implicating cellular mechanisms restricting the sites of spine turnover. These results
provide new insights into long-term synaptic dynamics and stability of synaptic structures in the adultbrain.

International Symposium on Development and Plasticity of Neural System

S-3
The force of dendritic-spine enlargement facilitating presynaptic exocytosis
Haruo Kasai
Laboratory of Structural Physiology, Faculty of Medicine and IRCN, The University of Tokyo

The majority of excitatory glutamatergic synapses are made on dendritic spines which enlarge during
learning. Since dendritic spines and the presynaptic terminals are tightly connected with the synaptic
cleft, the enlargement may have mechanical effects on presynaptic functions. We found that the fineand transient pushing of the boutons by a glass pipette markedly promoted an evoked neurotransmitter
release and the assembly of soluble N-ethylmaleimide-sensitive factor attachment protein receptor(SNARE) proteins, whose Förster resonance transfer (FRET) was measured with fluorescence
lifetime imaging (FLIM) in rat slice culture preparations. Surprisingly, both effects persisted over 20
min. The increased presynaptic FRET was independent of cytosolic calcium (Ca2+), but dependent on
the assembly of SNARE proteins and actin polymerisation in the boutons. Importantly, a low
hypertonic sucrose solution (20 mM, 0.5 kg/cm2) caused facilitatory effects on both the FRET andevoked release without inducing spontaneous release, making a striking contrast with a highhypertonic sucrose solution (300 mM) which induced exocytosis by itself. Finally, the spine
enlargement, induced by the two-photon glutamate uncaging, enhanced evoked release and FRET
only when the spines pushed the boutons by their elongation. Thus, we have found a mechanosensory and transduction mechanism in the presynaptic boutons.

International Symposium on Development and Plasticity of Neural System

S-4
Bridge over Troubled Synapses with Extracellular Scaffolding Proteins
Michisuke Yuzaki
Dean, Keio University Graduate School of Medicine
Professor, Department of Neurophysiology

Abnormal synaptic connections are believed to contribute to various neuropsychiatric,
neurodevelopmental and neurological disorders, such as schizophrenia, autism spectrum disorders andAlzheimer’s diseases. Thus, it is crucial to clarify the mechanisms by which synapses are formed,
maintained, and modified throughout life. Synaptic organizers, which mediate these processes, areclassified into secreted factors, such as Wnt and FGF, and cell adhesion molecules, such as neurexinsand neuroligins. Recently, a new class of synaptic organizers, secreted extracellular scaffolding
proteins (ESPs), such as C1q family proteins, LGI1, neuronal pentraxins and glial thrombospondins,have been discovered (Yuzaki M. Annu Rev Physiol 80:243-262, 2018). They serve as a scaffold forpre- and postsynaptic membrane proteins at the synaptic extracellular matrix. For example, Cbln1, a
prototype of the C1q family, is unique in that it is secreted from presynaptic neurons in an activitydependent manner (Ibata K et al., Neuron 102:1184-1198, 2019), and rapidly induces synapse
formation in the adult brain (Matsuda K et al., Science 328: 363-368, 2010; Elegheert J et al., Science
353:295-299, 2016). In contrast, Cbln2, a subfamily member of Cbln1, is reported to be secreted fromdendrites of pyramidal neurons in the hippocampus and controls glutamate receptor activity without
affecting synapse numbers (Dai et al., Nature 595:261-265, 2021). Furthermore, Cbln4 is reported toregulate inhibitory synapse formation between somatostatin-positive interneurons and pyramidal
neurons in the cortex (Favuzzi E et al, Science 363:413-417, 2019; Fossati M et al., Neuron 104:10811094, 2019). In this talk, I would like to summarize what is known so far about the C1q family anddiscuss how we could develop new therapeutic reagents against neuropsychiatric and neurologicaldisorders based on the known structures of known ESPs.

International Symposium on Development and Plasticity of Neural System

S-5
Brainstem circuits controlling arrest of movements
Ole Kiehn
Department of Neuroscience, University of Copenhagen, Denmark
Department of Neuroscience Karolinska Institute, Stockholm, Sweden

Arrest of ongoing movement is an integral part of executing motor programs. For intended or goaldirected movements, the arrest happens when a goal is reached e.g. reaching and grasping an object or
stopping locomotion once the desired location is reached. In other cases the movement arrest issudden as a reaction to changes in the environment. This talk will focus on work that has identified
neuronal brainstem circuits that bridge with executive motor circuits to implement motor arrests. It
will describe brainstem circuits in the medulla in mice that implement intended stop of locomotion
and also implement left-right directionality of the movement. The lecture will also report thediscovery of a distinct excitatory neuron population in the pedunculopontine (PPN) midbrain nucleithat induce global motor arrest with a phenotypical ‘pause and play’ motor pattern accompanied bybradycardia and slow respiratory frequency that is different from fear-induced freezing. The PPN‘pause and play’ circuit may be recruited in an arousal state needed to focus on environmental cues.
Our studies ascribe behavioral relevant motor arrests to distinct groups of excitatory brainstemcommand pathways.
This work was supported by The Novo Nordisk Foundation, European Research Council, and The
Lundbeck Foundation.

International Symposium on Development and Plasticity of Neural System

S-6
From the bench to clinical trials for regeneration enhancing Nogo-A antibodies forspinal cord injury
Martin E. Schwab
Institute for Regenerative Medicine IREM
University of Zurich, Zurich, Switzerland,
NovaGo Therapeutics Inc., Schlieren, Switzerland

Following injury of the mammalian brain or spinal cord, lesioned nerve fibers can spontaneously
grow and form new connections. This new ‘hardware’ can be fine tuned by intensive use and training
during rehabilitation. The regrowing fibers are spatially restricted, however, to often less than a mm.
Specific neurite growth inhibitory factors were found to restrict plastic and regenerative nerve fiber
growth in the adult CNS. The membrane protein Nogo-A is a well characterized, potent neurite
growth inhibitor in the CNS. Nogo-A activates an intracellular signalling cascade via multisubunit
receptor complexes. Function blocking antibodies against Nogo-A have been applied to rats andmacaque monkeys with spinal cord or cortical stroke lesions. In the spinal cord, injured fibers showedenhanced regenerative sprouting as well as long-distance regeneration. Spared fiber tracts showedenhanced compensatory sprouting. In animals with cortical strokes, intact-side corticobulbar or
corticospinal fibers crossed the midline, supplying functional innervation to the denervated brain stemand spinal cord under the influence of anti-Nogo-A antibodies. Functional recovery was improved,
including bladder functions. - Different antibodies against human Nogo-A were produced, optimized
and manufactured under GMP conditions. Their safety and tolerability after intrathecal infusion wastested in non-human primates. A Phase 1 clinical trial showed that repeated injection over 30 days iswell tolerated and safe in acute tetra- and paraplegic patients (Kucher et al., 2028). In a placebo
controlled, randomized Phase 2 trial, >96 severe, acute tetraplegic patients have been treated up to
now in a multinational European clinical trial network (NISCI). Arm – hand function (upper limb
motor score), lower limb function, bladder and autonomic functions, pain and quality of life scores arebeing evaluated over 6 mts. The trial will reach its projected number of patients in Q2/3-2022, andresults will be available from Q2-2023 on.

International Symposium on Development and Plasticity of Neural System

S-7
How do injured CNS neurons respond to axonal insults?
Zhigang He
Boston Children’s Hospital, Harvard Medical School

In adult CNS, an axonal damage often triggers retrograde neuronal death and regenerative failure.
This contributes to permanent functional deficits after CNS injury and to neurodegeneration indiseases such as glaucoma. Thus, there is a pressing need to understand how neurons respond to
injury. In adult mice, optic nerve crush (ONC) injury, which severs all axons of retinal ganglion cells(RGCs), results in massive death of axotomized RGCs and regenerative failure of survivors. With thismodel, our previous studies identified several critical regulators of neuronal injury responses, such as
PTEN/mTOR and/or SOCS3/STAT. However, major challenges remain. First, because some of theseinterventions have the risk of promoting tumor growth, it is critical to identify alternative and safe
pro-regenerative strategies. Second, while the pro-survival and pro-regeneration effects of theseavailable interventions are still partial, it is desirable to identify new molecular targets. My talk will
cover our recent progresses in these fronts. In the first part, I will present our results from single cell
RNA-seq analysis of RGCs with three interventions (deletion of Pten, deletion of Socs3, andoverexpression of CNTF), in collaboration with Josh Sanes’s group. Our studies define the injury
responses of 46 RGC types with these interventions in both transcriptional and cellular terms. We also
discovered several neuropeptides as potential pro-regeneration treatments. In the second part, I will
discuss the results from two non-biased genomic studies, in vivo CRISPR screen of transcription
factors and ATAC-seq/RNAseq, in collaboration with Dan Geschwind and Josh Sanes. Remarkably,
these independent analyses converged on a set of ATF/CEBP transcription factors as criticalregulators of survival. These TFs contribute to two degeneration transcriptional programs:
ATF3/CHOP preferentially regulate pathways activated by cytokines and innate immunity, whereas
ATF4/C/EBPγ regulate pathways engaged by intrinsic neuronal stressors. Thus, our results reveal
core transcription programs that transform an initial axonal insult into a degenerative result andsuggest novel strategies for treating neurodegenerative diseases.

International Symposium on Development and Plasticity of Neural System

S-8
Monosynaptic connections between corticospinal neurons and motor neurons
underlying manual dexterity in wild-type and ALS model mice.
Yutaka Yoshida
Burke Neurological Institute / Weill Cornell Medicine
Okinawa Institute of Science and Technology graduate University

Corticospinal neurons located in layer V of the sensorimotor cortex are the essential conveyers of motor
instructions controlling skilled movements. Corticospinal neurons form monosynaptic connections withmotor neurons (which are called corticomotoneuronal (CM) connections) only in primates, which play arole in independent finger movements. In contrast, corticospinal neurons are thought to form only
disynaptic connections with motor neurons through spinal interneurons in non-primate mammals.
However, we previously showed that CM connections are formed in early postnatal mice that are
eliminated by Sema6D-PlexA1 signaling during development. Adult PlexA1 mutant mice with CM
connections exhibit superior dexterity in forearm skilled movements over their littermate controls. Thissuggests that PlexA1 mutant mice may provide a better mouse model to study human motor disorders
compared to wild-type mice.
The amyotrophic lateral sclerosis (ALS) is a genetically complex disease with causal mutations in over
30 ALS-related genes. In patients with ALS, early symptomatic hallmarks include deficits in fine hand
movements. Indeed, CM connections have been suggested to be disrupted in early stages of ALS
patients. However, since wild-type mice do not have CM connections, it is not possible to study CM
connections using wild-type mice. Therefore, we crossed ALS mouse model (SOD1 mice) with PlexA1
mutant mice with CM connections. We found that CM connections may be disrupted at early
symptomatic timepoints in these mice, whereas disynaptic corticospinal connections are preserved. We
are currently investigating the mechanisms underlying disruption of CM connections in these mice.

S-9
How the brain works for recovery from spinal cord injury
Tadashi Isa
Department of Neuroscience, Graduate School of Medicine, Kyoto University
Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University

Spinal cord injury causes a devastating loss of sensory, motor and autonomic functions to thepatients and therapeutic strategies to improve these functions for enhancing their quality of life
is an urgent demand. In many cases, the injuries are partial, therefore promoting the functions of
the remaining part of the fiber tracts is considered to be the key for recovery. We have beenworking on the recovery of reaching and grasping movements of the forearm in the macaquemodel of the partial spinal cord injury. In case the injury is confined to the lateral funiculus
which transected the lateral corticospinal tract, the monkeys can recovery the ability of precisiongrip in several weeks through training. In this case, the spinal cord interneurons bridge theinjury and work for the recovery. In addition, very dynamic change in the circuit operation
occurs at the cortical level. In addition to the contralesional motor cortex, ipsilateral primary
motor cortex (M1) is activated during the early stage (~1 month after injury) by thecontralesional M1 via the corpus callosum and contribute to the recovery. In the later stage (3-4months after injury), the bilateral premotor cortices (PM) contribute to the recovery.
Furthermore, the mesolimbic system including the nucleus accumbens facilitates the motor
cortex and promotes recovery. In contrast, in case of the subhemisection (larger lesion), usually
the recovery of hand movements is slow and very limited even at 6 months after injury.
However, through intensive training and weekly extensive electrical stimulation of bilateral PM
and M1, the precision grip never recovered but coarse grip considerably recovered in several
weeks after injury. In this case, the bilateral PM and M1 are highly disinhibited and interactedwith each other, and the corticospinal tract from the contralesional M1 exhibited a massive rerouting; 20-30% of the corticofugal fibers became uncrossed, descended in the contralesionalside, crossed the midline caudal to the lesion and reached the gray matter including the motor
nuclei of the affected hand/arm muscles, amazing plasticity in the adult brain. These basic

animal experimental studies gave us several conceptual updates for development of the future
therapeutic strategies.
References
Suzuki et al. (2020) Cereb Cortex 30: 3259-3270, Chao et al. (2019) Cereb Cortex 29:3059-3073,
Isa (2019) Ann Rev Neurosci 42:315-335, Isa (2017) Trends in Neurosci 40:625-636, Tohyama
et al. (2017) Proc Natl Acad Sci USA 114:604-609, Sawada et al. (2015) Science 350: 98-101,
Kinoshita et al. (2012) Nature 487: 235-238, Nishimura et al. (2007) Science 318: 1150-1155.

International Symposium on Development and Plasticity of Neural System

S-10
Disease Modeling using Marmosets with Germ Line Modification and In Vivo Genome
Editing
Hideyuki Okano
Laboratory for Marmoset Neural Architecture, RIKEN Center for Brain Science, Saitama, Japan
Department of Physiology, Keio University School of Medicine, Tokyo, JapanThe common marmoset (Callithrix jacchus) is a small New World primate that has been extensively
used as biomedical research models. There is also an increasing interest in common marmoset in
Brain Science and as appropriate models for major human brain disorders (Okano, Annu Rev
Neurosci, 2021; Okano et al., Neuron, 2016; Grillner et al., Nat Neurosci, 2016).
We have been working with a number of collaborators to build a platform for marmoset brain
science research. In 2009, we succeeded in generating the world's first genetically modified (GM)marmoset with germline transmission by lentiviral mediated transgenesis (Sasaki et al., Nature, 2009),
and in 2015, we succeeded in determining the detailed sequence of the entire marmoset genome using
next-generation sequencing (Sato et al., Sci Rep, 2015). On this basis, we successfully createdindividual genome-edited marmosets (GM) using lentiviral mediated transgenesis (Sasaki et al.,Nature, 2009), and in 2015, we successfully sequenced the entire genome of a marmoset using a nextgeneration sequencer (Sato et al., Sci Rep, 2015). In 2015, we successfully sequenced the entire
genome of the marmoset using next-generation sequencing (Sato et al., Sci Rep, 2015), and on thisbasis, we successfully created genome-edited marmosets (Sato et al., Cell Stem Cell, 2016).
In the present talk, I wish to mention our recent data of generation of transgenic marmoset models ofneurodegenerative diseases, including Parkinson disease (PD) which overexpressed the mutant formof -synuclein suing lentiviral vector. The PD model marmoset showed stage-dependent progressionof the disease, such as sleeping disturbance followed by motor deficit. In addition, I will mention amodel marmoset of a neurodevelopmental disorder, the Rett syndrome, obtained by genome editing of
MECP2 gene. Abnormalities in brain structure and function in these marmoset models may accelerate
discovery of disease biomarkers and mechanisms toward translation (Okano et al., Neuron, 2016).

International Symposium on Development and Plasticity of Neural System

S-11
Rhesus Macaque vs Rat Divergence in the Corticospinal ProjectomeMark H. Tuszynski
University of California, San Diego

We used viral intersectional tools to map the projectome of corticospinal neurons associated with finedistal forelimb control in Fischer 344 rats and rhesus macaques. In rats, we found an extraordinarily
diverse set of collateral projections from corticospinal neurons to 23 different brain and spinal
regions. Remarkably, the vast weighting of this “motor” projection was to sensory systems in both thebrain and spinal cord, confirmed by optogenetic and trans-synaptic viral intersectional tools. In
contrast, rhesus macaques exhibited far heavier and narrower weighting of corticospinal outputs
toward spinal and brainstem motor systems. Thus, corticospinal systems in macaques primarily
constitute a final output system for fine motor control, whereas this projection in rats exerts a multimodal integrative role that accesses far broader CNS regions. Unique structural-functionalcorrelations can be achieved by mapping and quantifying a single neuronal system’s total axonal
output and its relative weighting across CNS targets.

International Symposium on Development and Plasticity of Neural System

S-12
iPS cell-based therapy for Parkinson’s disease
Jun Takahashi
Kyoto University, Center for iPS Cell Research and Application, Kyoto, Japan

Human induced pluripotent stem cells (iPSCs) can provide a promising source of midbrain
dopaminergic (DA) neurons for cell replacement therapy for Parkinson's disease (PD). Towards
clinical application of iPSCs, we have developed a method for 1) scalable DA neuron induction onhuman laminin fragments and 2) sorting DA progenitor cells using a floor plate marker, CORIN. The
grafted CORIN+ cells survived well and functioned as midbrain DA neurons in the 6-OHDA-lesioned
rats, and showed the minimal risk of tumor formation. In addition, we performed a preclinical study
using primate PD models. Regarding efficacy, human iPSC-derived DA progenitor cells survived andfunctioned as midbrain DA neurons in MPTP-treated monkeys. Furthermore, regarding safety, cells
sorted by CORIN did not form any tumors in the brains for at least two years. Based on these results,
we have started a clinical trial to treat PD patients at Kyoto University Hospital in Kyoto, Japan, in
2018. The trial evaluates the safety and efficacy of transplanting human iPS cell-derived DAprogenitors into PD patients' putamen. We implant approximately 5 million cells into every sevenpatients and observe for two years. The trial is now ongoing without any trouble.

International Symposium on Development and Plasticity of Neural System

S-13
Genetic strategies to create stereotyped arbor wiring
Adrian W Moore
RIKEN Center for Brain Science, Wako, Japan

Neurons have stereotyped dendrite and axon arbors. These scaffold synaptic connectivity, and control
computation of information by the cell. From vertebrates to invertebrates, dendrite arbor wiring
patterns are genetically programmed; our laboratory asks how these programs are decoded. We
approach this by examining arbor differentiation as a sequential and changing process, in which
different sequences or durations of cell behaviors create specialized wiring pattern outcomes. To
reveal the molecular control processes, we integrate in vivo high spatiotemporal resolution time-lapse
imaging and quantitation of arbor differentiation, with state-of-the-art transcriptomics. Our recent
studies using Drosophila peripheral sensory neurons as an experimental system, have led to a newmodel for stereotyped arbor specification; transcription factors encode the growth and branching
dynamics of arbor differentiation by setting the identity, spatial organization, and amplitude of
microtubule generation events in the neuron.

International Symposium on Development and Plasticity of Neural System

S-14
Cytoskeletal forces driving neuronal migration in 3D brain tissues
Mineko Kengaku
Kyoto University Institute for Advanced Study, Institute for Integrated Cell-Material Sciences (KUIAS-iCeMS)
Kyoto, Japan

After the last cell division in the germinal zone, newborn neurons migrate from the birthplace to thespecific layer in the cortex where they are integrated in functional neural circuits. Delivery of thenucleus which is the largest and stiffest cargo presents the biggest physical challenge for migratingneurons to pass through the crowded neural tissue. It has been shown that the nuclear delivery isorchestrated by the pulling force of cytoplasmic dynein, the minus-end directed microtubule motor,
and the contractile force of actomyosin. However, the mechanisms of how cytoskeletal forces arecoordinated and converted to actual nuclear behaviors remain unclear.
By using high-resolution live imaging, we attempt to visualize the microtubule- and actin-dependent
force in migrating cerebellar granule cells. Unlike the prevailing view that dynein is the predominantmicrotubule motor driving nuclear migration, we demonstrated that an opposing force by kinesin(KIF5) is also required for normal neuronal migration. Dynein and kinesin dynamically dock to small
points of the nuclear envelope and drive complex nuclear dynamics including pinching, rotation andtranslocation and thereby enable nuclear migration in narrow interstitial spaces. In contrast to thesteering forces of the microtubule motors, actomyosin instead exerts strong contractile force in thefront and rear of the nucleus. We have found that neurons sense the space confinement via amechanosensor Piezo1and switch the force generation mechanism by recruiting distinct actomyosin
networks. Thus, neurons are equipped with multiple cytoskeletal engines and migrate through diverse
extracellular environment by switching the migration modes.

International Symposium on Development and Plasticity of Neural System

S-15
New (and small) regulators of cerebral cortex size and folding during evolution
Victor Borrell
Institute of Neuroscience, CSIC-UMH, San Juan de Alicante, Spain

The evolutionary expansion and folding of the mammalian cerebral cortex resulted from theamplification of neural stem and progenitor cells during embryonic development. This wassecondarily reversed in some lineages like rodents, leading to smaller brains with a smooth cortex.
The genetic bases of these complex evolutionary dynamics remain unclear. While brain expansion in
the recent human lineage is in part explained by the emergence of few new genes, mounting evidence
points at the differential regulation of conserved genetic mechanisms as being central in the evolutionof neurogenesis and brain size across vertebrates. I will discuss our findings in mouse showing thecentral role of microRNAs in the regulation of gene expression in the early embryonic cerebral cortex,
with a critical impact on progenitor cell amplification and neurogenesis, and the consequences of theirderegulation in pediatric brain cancer. Our recent work further shows that the small non-coding RNA
MIR3607 has a positive influence on cortical progenitor cell amplification, by dramatically activating
itself beta-Catenin signaling via blockade of APC expression. Importantly, MIR3607 is expressed athigh levels in germinal layers of the embryonic cortex of primates and carnivores, where it promotes
progenitor amplification, but was secondarily lost in the rodent lineage, leading to smaller progenitor
pools and, consequently, to the reduction in size and folding of their cortex. Finally, I will present ourlatest findings on the epigenetic regulation of cortex folding in ferret, where we identify well-known
transcription factors as unsuspected key players in this process. Our results show the central
importance of mechanisms of gene expression regulation in the evolution of embryonic corticaldevelopment, and its consequences on cortex size and folding.

International Symposium on Development and Plasticity of Neural System

S-16
Mechanisms of neuronal subtype transition and integration in the cerebral cortex
Carina Hanashima
Department of Biology, Waseda University
Center for Advanced Biomedical Sciences

The functional integrity of the brain system relies on the precisely coordinated production of diverse
neurons and their placement along the three-dimensional axis. Specifically in the cerebral cortex,
progenitor cells produce distinct neuronal subtypes in a stereotypical order and establish a six-layer
structure, which are further modified into functional areas. A prevailing view concerning theneurogenesis of the neocortex is that neural stem cells undergo successive rounds of asymmetric cell
divisions to produce the principal layer subtypes: preplate, deep-layer, and upper-layer neurons,
through a progressive restriction in cell competence. Consistent with this view, we previously showedthat transcriptional regulatory network plays a central role in establishing early cell identity andswitching neurogenesis. However, recent studies have also indicated that the specification andintegration of neocortical neurons relies on communication between distinct cell types, in addition to
intrinsic transcriptional regulation. I will present our findings on the mechanisms by which
neocortical subtype identities establish in the neocortex, by manipulating gene expression and numberof neurogenesis in the developing mouse cortex. Our results indicate that neocortical progenitors
integrate both intrinsic and extrinsic cues to generate distinct layer neurons, a system which ultimatelybalances the production of neocortical subtypes during development and possibly evolution.

International Symposium on Development and Plasticity of Neural System

S-17
Characteristics of subplate neuron molecular expression elucidated by single-cell andspatial transcriptome analysis
Chiaki Ohtaka-Maruyama
Developmental Neuroscience Project, Tokyo Metropolitan Institute of Medical Science (TMIMS), Tokyo, Japan

In the mammalian neocortex, a large number of neurons are precisely arranged in an ordered 6layered structure inside out. This structure is formed by the sequential generation of neurons and theirmigration toward the brain surface, radial neuronal migration. We previously reported that subplate
neurons (SpNs), which are one of the first-born and mature types of neurons in the developing
neocortex, play an essential role in regulating radial migration. We revealed that SpNs exhibit
spontaneous calcium oscillations at E15 and actively extend processes to contact newly born
multipolar migrating neurons (MpNs) via synaptic structure. SpNs play a critical role in establishing
the first neural circuit between the thalamus and cortex in the mid-embryonic and perinatal stages
during neocortical development, suggesting their necessity in the period of cortical formation.
Although most SpNs die postnatally, the remaining fraction of SpNs located in layer 6b in adultmammals may continue to fire spontaneously and play a role in brain activity during sleep. To
elucidate the function of SpNs in more detail, we are now characterizing their subpopulations using a
SpN-specific transgenic mouse line (Lpar1-EGFP) or Cre-ERT2 mouse line (D1B-Cre). Single-cell
analysis and Visium spatial transcriptome analysis revealed novel molecular markers of SpNs in theembryonic stage. The result supported the idea that SpNs consist of heterogeneous cell populations
and that each subpopulation has distinct roles in the formation and function of the neocortex.

International Symposium on Development and Plasticity of Neural System

S-18
Neurogenesis in the adult human hippocampus
Jonas Frisén
Department of Cell and Molecular Biology, Karolinska Institute, Sweden

Neurogenesis in the adult hippocampus has been described in many mammals, but is challenging tostudy in humans. The generation of new neurons in adult humans has been demonstrated by BrdU
labelling and 14C retrospective birth dating. In mice, the new neurons are generated by neural stem
cells, via intermediate progenitor cells. Several studies have demonstrated the presence of neuralprogenitor cells in the adult human dentate gyrus as well as changes in their numbers over the lifespanas well as in pathological conditions. However, a few recent studies have failed to find progenitor
cells in the adult human hippocampus either by immunohistochemistry or snRNA-seq, prompting
them to suggest that neurogenesis is absent in adult humans, fueling a new wave of controversy in thisresearch field.
We have analyzed the human hippocampus by large scale snRNA-seq in 26 subjects 0-78 years old
and identified a neurogenic cell trajectory from stem cell to immature neuron present from birth tohigh age. We distinguish different cell stages, their markers and gene regulatory networks and explain
why others have failed to detect these cells. The number of cells of all stages of neurogenesis ishighest in early childhood and is maintained at lower levels throughout adulthood into high age,
underlying adult neurogenesis. The identification and molecular characterization of the cells
underlying hippocampal neurogenesis through the human lifespan will aid studies on the regulation
and role of this process in health and disease.

International Symposium on Development and Plasticity of Neural System

S-19
Neurogenesis in the dentate gyrus of the hippocampus as a continuous developmental
process across the lifespanHongjun SongDepartment of Neuroscience, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.

Immature dentate granule cells arising from adult hippocampal neurogenesis contribute to plasticity
and unique brain functions in rodents and they are dysregulated in many human neurologicaldisorders. Using genetic clonal lineage-tracing, we identified a pool of neural stem cells that exhibit
similar molecular and epigenetic characteristics and continuously generate dentate granule neurons
throughout life in the mouse hippocampus. Single-cell RNA-seq analysis further reveals a transition
from active to quiescent neural stem cell state during the early postnatal stage followed by acontinuous maturation process. Rather than categorize hippocampal neurogenesis into two stages of“embryonic neurogenesis” vs. “adult neurogenesis”, we propose a continuous model of neurogenesis
suggesting that dentate gyrus development is a life-long process. We further provide evidence for thepresent of immature dentate granule neurons and identify their molecular characteristics in the humanhippocampus across the lifespan.

International Symposium on Development and Plasticity of Neural System

S-20
Cell cycle arrest determines adult neural stem cell ontogeny
Yujin Harada1 and Yukiko Gotoh1,2
Graduate School of Pharmaceutical Sciences, 2International Research Center for Neurointelligence (WPIIRCN), The University of Tokyo, Japan
1

Quiescent neural stem cells (NSCs) in the adult mouse brain are the source of neurogenesis that
regulates innate and adaptive behaviors. Adult NSCs in the subventricular zone are derived from a
subpopulation of embryonic neural stem-progenitor cells (NPCs) that is characterized by a slower cell
cycle relative to the more abundant rapid cycling NPCs that build the brain. Yet, how slow cell cycle
can cause the establishment of adult NSCs remains largely unknown. Here, we demonstrate that
Notch and an effector Hey1 form a transcriptional module that is upregulated by cell cycle arrest in
slowly-dividing NPCs. In contrast to the oscillatory expression of the Notch effectors Hes1 and Hes5
in fast cycling progenitors, Hey1 displays a non-oscillatory stationary expression pattern andcontributes to the long-term maintenance of NSCs. These findings reveal a novel division of labor in
Notch effectors where cell cycle rate biases effector selection and cell fate.

International Symposium on Development and Plasticity of Neural System

S-21
Defining mammalian neural stem cell transitions and niches from embryogenesis toadulthood
Freda Miller
Associate Director, Michael Smith Laboratories
Professor, Dept. Medical Genetics
University of British ColumbiaThis lecture will describe our recent work focusing on mammalian forebrain neural stem cells to
address two key questions in the field of neural stem cell biology. First, how is the mammalian poolof adult dormant neural stem cells generated developmentally and second, how does the neural stem
cell niche evolve over developmental time and following injury? The lecture will also discuss
potential insights this work provides into the reactivation of adult neural stem cells following
demyelinating injuries.

International Symposium on Development and Plasticity of Neural System

S-22
Postnatal neuronal migration in health and disease
Kazunobu Sawamoto
Institute of Brain Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
National Institute for Physiological Sciences, National Institutes of Natural Sciences, Okazaki, Japan

New neurons are continuously generated from neural stem cells in the ventricular-subventricular zone
(V-SVZ) of the walls of the lateral ventricles in the postnatal mammalian brain. These new neurons
migrate toward their destinations, where they are differentiated into mature neurons involved in themaintenance and plasticity of brain tissues. After brain injuries, new neurons migrate toward the
injured area for regeneration. However, they generally terminate the migration before reaching thelesion site unless their intrinsic capacity is modified or the environment is improved. It is important tounderstand which factors impede neuronal migration for functional recovery of the brain. Neuronalmigration is restricted by the meshwork of activated astrocytes in and around the lesion. To movetoward the lesion, new neurons form chain-like aggregates and migrate along blood vessels, which
increases their migration efficiency. Radial glia are polarized embryonic neural stem cells, which
guide newly generated neurons by providing their fibers as a migratory scaffold. Radial glial fibers
are maintained for an extended period in the injured neonatal mouse brain and provide a scaffold on
which V-SVZ-derived new neurons migrate toward the injured cerebral cortex. New neuron migration
toward the lesion can be promoted by clearing the path of astrocytic processes, and by inserting
artificial scaffolds that mimic the endogenous scaffolds. These findings suggest that strategies
designed to help migrating neurons reach the lesion may improve stem/progenitor cell-based therapies
for brain injury. This talk will highlight similarities and differences in the mechanisms of postnatal
neuronal migration under physiological and pathological conditions to provide novel insights into
endogenous neuronal regeneration.

International Symposium on Development and Plasticity of Neural System

S-23
Genomic Insights into Early Human Brain Development, Evolution, and Disease
Arnold Kriegstein
Department of Neurology, Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research,
University of California, San Francisco, San Francisco, California

The human cerebral cortex is more than three times expanded compared to our closest non-humanprimate relatives. The cortex emerges from an initially pseudostratified neuroepithelium that gives
rise to radial glia, the neural stem cells of the cortex. A number of subtypes of radial glia have been
identified, and single cell RNA sequencing (scRNAseq) has contributed to a novel model of primate
corticogenesis, highlighted human-specific features of cortical development, suggested a relationshipbetween oRG cells and brain tumors, and provided a benchmark for in vitro organoid models of brain
development and disease. We have begun to characterize the molecular populations of cellularsubtypes that exist at the onset of neurogenesis. Our single-cell transcriptomic and in-situ data suggestthat early cortical areal patterning is strongly defined by the mutual exclusion of strong frontal or
occipital gene expression signatures, with the specification of areas between these two poles arisingfrom the resulting gradients at later developmental timepoints. Thus, we find evidence supporting theexistence of a cortical protomap at the extremities, but also support for the protocortex hypothesis torefine spatial identity between the poles. Using velocity analysis, we find that major signaling
pathways including Notch, Wnt, and mTOR drive the specification and maintenance ofneuroepithelial stem cells and radial glia. Comparison of these progenitor populations to organoidsystems highlights important differences and suggests that manipulation of these signaling pathways
may improve in vitro models of early progenitor populations. Overall, we provide a comprehensive
molecular and spatial atlas of early stages of human brain and cortical development at the onset ofneurogenesis.

International Symposium on Development and Plasticity of Neural System

S-24
Analysis of neural stem cell regulatory mechanisms using optogenetics
Itaru Imayoshi
Research Center for Dynamic Living Systems, Graduate School of Biostudies, Kyoto University
Institute for Frontier Life and Medical Sciences, Kyoto University

The mammalian brain consists of a complex ensemble of neurons and glial cells. Their production
during development and remodeling is tightly controlled by various regulatory mechanisms in neuralstem cells. Among such regulations, basic helix-loop-helix (bHLH) factors have key functions in the
self-renewal, multipotency, and fate determination of neural stem cells. Here, we highlight theimportance of the expression dynamics of bHLH factors in these processes. We propose themultipotent state correlates with oscillatory expression of several bHLH factors, whereas thedifferentiated state correlates with sustained expression of a single bHLH factor. We also developed
new optogenetic methods that can manipulate gene expressions in neural stem cells by light. We used
this technology to manipulate the growth and fate-determination of neural stem cells. We are also
analyzing dynamic changes in downstream gene expressions and cellular states caused by systematic
light-induced manipulations of bHLH transcription factors.

International Symposium on Development and Plasticity of Neural System

S-25
Exploring the relationship of progenitor subtypes in and between gyrencephalic species
at the single cell level
Fumio Matsuzaki
RIKEN Center for Biosystems Dynamics Research

The expansion of the mammalian brain during evolution are thought to largely depend on the emergenceof a new germinal layer (the outer subventricular zone: OSVZ) and great heterogeneity of progenitor
cell types. As distinct subtypes of neural progenitors may generate different populations of progenies,
it is crucial to characterize the spatial and temporal pattern of individual progenitor types and theirterminal fates.
in vivo genetic manipulation and single-cell transcriptome (scTCM) analyses are two powerfulapproaches to understand molecular and cellular properties of particular cells. scTCM of the humanbrain has been extensively performed, revealing transcriptional signatures of diverse progenitor
populations. However, in vivo mechanisms underlying the development of human radial glial (RG) cells
remained less explored due to a limited experimental access. Studies using brain organoids turned out
to face problems to recapitulate molecular properties of cell-types in human brain development.
Under this situation, a valuable animal model to overcome difficulties in studying the human brain is
the ferret (Mustela putorius furo), a carnivore with gyrencephalic features such as the OSVZ, forming
a complex and folded brain, and also available for in utero electroporation (Kawasaki et al., 2012) andde novo genome-editing (Tsunekawa et al., 2016). Yet, the temporal pattern of molecular signatures offerret progenitors remained largely unexplored at a high resolution. We investigated progenitor
subtypes in the ferret by scTCM along the developmental course, and compared them with human
information to reveal common and species-specific cell-types during the development of the complex
brain. We also manipulated progenitors in ferrets by several approaches to understand subtype
relationships and fates of neural progenitors.

International Symposium on Development and Plasticity of Neural SystemS-26
A cerebral organoid model for Tuberous sclerosis identifies human-specific aspects ofbrain development
Oliver L Eichmüller 1, 2, Nina S Corsini 1, Ábel Vértesy 1, Ilaria Morassut 1, Theresa
Scholl 3, Victoria-Elisabeth Gruber 3, Angela M Peer 1, Julia Chu 4, Maria
Novatchkova 1, Johannes A Hainfellner 5, Mercedes F Paredes 4, Martha Feucht 3,Jürgen A Knoblich 1, 5
1Institute of Molecular Biotechnology (IMBA), Austrian Academy of Sciences, Vienna Biocenter (VBC),
Vienna, Austria.
2
University of Heidelberg, Heidelberg, Germany.
3
Department of Pediatric and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.
4
Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
5
Department of Neurology, Medical University of Vienna, Vienna, Austria.

The human brain is unique in size and complexity, but also the source of some of the mostdevastating human diseases. Cerebral organoids derived from patients suffering fromneurodevelopmental disease can recapitulate the developmental defects leading to those diseases
and allow us to disentangle the mechanistic complexity of disorders like Epilepsy and Autism.
We were able to recapitulate the histological characteristics of Tuberous sclerosis, a severe
form of epilepsy caused by genetic upregulation of mTOR signaling. We show that different
culture conditions can be used to recapitulate either tumor formation or generation of giant
neurons, both features that are diagnostic of TSC patient brains. Unlike all mouse models,organoid models display those features even in heterozygous patients without the need for lossof heterozygosity. Using single cell transcriptomics, we identify the CLIP cells (caudal lateinterneuron progenitors), a previously unknown human specific progenitor cell located in thecaudal ganglionic eminences. Our data suggest that CLIP cells are responsible for the massive
postnatal migration of interneurons into the prefrontal cortex that is seen in humans but not inrodents, adding functional relevance to this recently discovered phenomenon. Our results
indicate that organoid models can fundamentally change widely accepted human disease
concepts and lead to fundamental insights into the human-specific aspects of brain
development.

International Symposium on Development and Plasticity of Neural System

S-27
Human-specific temporal mechanisms of brain development.
Pierre Vanderhaeghen
VIB-KU Leuven Center for Brain & Disease Research, Leuven, Belgium.

The human brain, in particular the cerebral cortex, has undergone rapid expansion and increased
complexity during recent evolution.
One striking feature of human corticogenesis is that it is highly protracted in time, from prenatal stagesof neurogenesis (taking months instead of days in the mouse), to postnatal stages of neuronal maturationand circuit formation (taking years instead of weeks in the mouse). This prolonged development isthought to contribute in an important fashion to increased cortical size, but also enhanced circuit
complexity and plasticity. In vitro and xenotransplantation models indicate that the developmental
timing of corticogenesis is largely intrinsic to cortical progenitors and neurons. The underlying
mechanisms include human-specific molecular and cellular properties, which may underlie humansensitivity to certain brain diseases.

International Symposium on Development and Plasticity of Neural System

S-28
Lineage recording in human cerebral organoids
J. Gray Camp
Roche Institute for Translational Bioengineering (ITB), Roche Pharma Research and Early Development, Roche
Innovation Center Basel, Switzerland

Induced pluripotent stem cell (iPSC)-derived organoids provide models to study human organ
development. Single-cell transcriptomics enable highly resolved descriptions of cell states withinthese systems; however, approaches are needed to directly measure lineage relationships. Here weestablish iTracer, a lineage recorder that combines reporter barcodes with inducible CRISPR–Cas9
scarring and is compatible with single-cell and spatial transcriptomics. We apply iTracer to explore
clonality and lineage dynamics during cerebral organoid development and identify a time window offate restriction as well as variation in neurogenic dynamics between progenitor neuron families. We
also establish long-term four-dimensional light-sheet microscopy for spatial lineage recording in
cerebral organoids and confirm regional clonality in the developing neuroepithelium. We incorporate
gene perturbation (iTracer-perturb) and assess the effect of mosaic TSC2 mutations on cerebral
organoid development. Our data shed light on how lineages and fates are established during cerebral
organoid formation. More broadly, our techniques can be adapted in any iPSC-derived culture system
to dissect lineage alterations during normal or perturbed development.

International Symposium on Development and Plasticity of Neural System

S-29
Neural Development in Stem Cell Culture
Mototsugu Eiraku
Institute for Frontier Life and Medical Sciences, Kyoto University
Institute for the Advanced Study of Human Biology, Kyoto University

Pluripotent stem cells (such as ES cells and iPS cells) can, in principle, differentiate into all cell types
that make up our body. In a last decade, a technology that induces the differentiation of pluripotent
stem cells into desired cell types by mimicking the environment of the developing organ in a culture
dish has greatly developed. We have developed a method to induce various neural regions such ascerebral cortical tissue and retinal tissue from pluripotent stem cells (cerebral organoids and retinalorganoids), and have studied the molecular basis of self-organization in the pattern formation andmorphogenesis. In this talk, I will introduce a new means to form a tissue with the function as acircadian clock center, capable of sustaining stable gene expression oscillations in a 24-hour cycle formore than 20 days from pluripotent stem cells. In addition, I will talk about induction of humanolfactory sensory epithelium organoids and its application to elucidate the mechanism of olfactoryabnormality caused by SARS-CoV2 infection.

International Symposium on Development and Plasticity of Neural System

S-30
Emotional arousal enhances perceptual memory through amygdalo-cortical input
during NREM sleep
Masanori Murayama
RIKEN Center for Brain Science, Wako, Japan

Emotional arousal is thought to enhance memory consolidation through projections from thebasolateral amygdala (BLA) to sub-/cortical regions. However, it is still unclear where and how the
BLA interacts to enhance memory consolidation. Furthermore, even the question of whether rapideye-movement (REM) or non-REM (NREM) sleep state is essential for enhancing memory
consolidation by emotional arousal has not been settled. Using electrophysiological recordings andmanipulating a BLA-cortical circuit during a perceptual-emotional associative learning task, we reportthat BLA neurons store emotional memory and enhance perceptual memory through BLA inputs tothe cortex during NREM sleep. In the associative learning task, male mice learned the floor texture
paired with a female in a cup on the floor. Male mice that had associated the floor texture with thefemale showed a more extended retention period of the floor texture memory than mice that had not
met the female. We previously reported that inputs from the secondary motor cortex (M2) to theprimary somatosensory cortex (S1) play crucial roles in texture memory consolidation. Based on the
results, anatomical studies indicated a strong projection from the BLA to the M2 but weak to the S1.
Immunohistological analysis of activity-dependent early gene expression revealed that the female
presentation to male mice during the task activates BLA neurons. Chemogenetic inactivation of M2projecting BLA neurons during the post-learning period impaired female memory consolidation.
Interestingly, the inactivation of this circuit did not impair texture memory but did suppress the
texture memory enhancement. Furthermore, simultaneous extracellular recording from the BLA, theM2, and the S1 revealed that the female presentation enhanced reactivations of the inter-regional cellensembles during NREM but not during REM sleep. Finally, optogenetic inactivation of BLA inputs
at the M2 during NREM sleep suppressed the texture memory enhancement but not the female
memory. A similar circuit manipulation during REM sleep did not impair any behavioral parametersin our observations. These results demonstrate that BLA-M2 inputs during NREM sleep have a causal
role in enhancing perceptual memory consolidation by emotional arousal.

International Symposium on Development and Plasticity of Neural System

S-31 TBC
Talk Title
Speaker nameAffiliation(s)International Symposium on Development and Plasticity of Neural System

S-32 TBC
Talk Title
Speaker nameAffiliation(s)International Symposium on Development and Plasticity of Neural System

S-33
Discovery of neurons monitoring whether the prediction comes true in the brain ofzebrafish escaping in the virtual reality space
Hitoshi Okamoto
RIKEN Center for Brain Science

Based on the recent finding that the brain of adult zebrafish, a small tropical fish, is small andrelatively simple, but shares the most basic structure with that of the mammalian brain, we havedevised a new virtual reality setup specifically for adult zebrafish and studied the time-lapsechange of neuronal activity in the brain of zebrafish swimming in this device as they learn to
avoid danger. As a result, we found in the part of the zebrafish brain that corresponds to the
cerebral cortex of mammals that repeated avoidance training produces a cluster of neurons
whose activity represent the prediction error between the training-informed prediction of the
optimal future situation and the actual view, and that the fish behaves in a way that minimizes
the activity of this cluster of neurons, resulting in the most efficient escape behavior. In thismeeting, I would like to report our recent advance in the study of how such prediction andprediction error is generated by training, and how it is implemented for the improvement of
behaviors by observing neural activities of the deeper parts of the telencephalon.

International Symposium on Development and Plasticity of Neural System

S-34
Variable axon connectivity of song memory ensembles in developmental zebra finch
song learning
Yoko Yazaki-Sugiyama
Okinawa Institute of Science and Technology (OIST) Graduate University
WPI-IRCN, the University of Tokyo

Songbirds learn to sing as humans learn to speak during development. They first listen and memorize
their tutors’ vocalization in the auditory learning period, and then in the following sensorimotor
learning period, they practice their motor skills (vocalization) based on tutor vocal memories.
Recently we reported that the tutor song memory ensemble stored in the caudomedial nidopallium(NCM), analogous to mammalian higher auditory cortex in zebra finches. However, the brain
developmental principles governing this time-sensitive sensorimotor learning are poorly understood.
Here we performed a zebra finch whole brain connectome mapping across the developmental songlearning period by the combination of whole brain tissue clearing and viral labeling of axonal
projections from a cluster of NCM neurons activated by tutor song exposure. We found previously
unreported axonal projections to HVC AIV, Area X and HVC-Shelf in juveniles in the sensorimotor
learning period. In contrast in the adult when their songs became stereotyped, we observed a selective
axonal disconnection between NCM and HVC, the pre-motor song output area. Viral ablation of theNCM neuronal memory ensemble in juveniles prevented song learning. Conversely, when juvenile
birds learned two songs sequentially, from the first tutor of a different species and then from a second
one of their own species, memory ensembles of both tutors and their NCM-HVC connections
remained in the adults. The findings show that the NCM memory ensemble makes a transientconnection to HVC for juvenile song learning and while a permanent adult connection is required to
encode two songs. These results demonstrate dynamic interarea neuronal connectivity for two step,sensory and sensorimotor, acquisition of individually unique songs in zebra finches. Extensive
experiences in juvenile period might increase a capacity of neuronal circuits in the adults that may
have implications for neural mechanisms of human second language learning.

International Symposium on Development and Plasticity of Neural System

S-35
Lateral inhibition signals for synaptic competitions
Takeshi Imai
Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

In developing brains, neurons initially form excessive connections and then remodel them to form
precise neuronal circuitry. Inter-and intra-neuronal synaptic competitions have been postulated, but
their nature has remained elusive. In the mouse olfactory bulb, mitral cells initially extend multiple
dendrites to multiple glomeruli, but developmentally they prune all but single primary dendrites. It
has remained unknown how they establish just one primary dendrite. Here we show that geneticallysilencing neuronal activity in mitral cells, but not neurotransmission from olfactory sensory neurons,
precludes developmental dendrite pruning. Glutamatergic spontaneous activity generated within theolfactory bulb is essential. We also find that the activity-dependent dendrite pruning is mediated by
NMDARs and Rho GTPases. FRET imaging experiments show that glutamatergic synaptic inputs via
NMDARs locally suppress RhoA, but globally activate it within a mitral cell to selectively prune
weaker dendrites. Thus, activity-dependent long-range lateral inhibition via Rho GTPases establishes
just one primary dendrite in a mitral cell.

International Symposium on Development and Plasticity of Neural System

S-36
Control of astrocyte dispersion in the developing cerebral cortex
Kazunori Nakajima
Department of Anatomy, Keio University School of Medicine, Tokyo, Japan

Astrocytes are among the most abundant cell types in the mammalian brain. They play essential roles
not only in the mature brain but also during development, including in neural network formation by
regulating synapse formation, maturation, and elimination. Despite their importance, the mechanisms
involved in astrocyte production and distribution throughout the brain during development are poorly
understood. Here, we showed that, during development of the mouse cerebral cortex, proliferative
astrocyte progenitors migrated by switching between a newly identified migration mode, erratic
migration, and a blood vessel-guided migration mode. During erratic migration, astrocyte progenitors
moved rapidly and almost randomly within the intermediate zone and the cortical plate (CP). Thesecells divided frequently, and the daughter cells exhibited the same irregular pattern. Astrocyte
progenitors also adopted blood vessel-guided migration, especially in the superficial CP. These cell
behaviors of astrocyte progenitors were also confirmed using two-photon in vivo imaging of intact
living embryos. Interestingly, angiogenesis itself was supported by astrocyte progenitors that bridged
neighboring blood vessels during blood vessel-guided migration. The progenitors involved in these
two migratory behaviors were generated in the prenatal stages and eventually differentiated into
protoplasmic astrocytes in the cortical gray matter, whereas fibrous astrocytes in the white matter
were generated postnatally. When the molecular mechanisms that underlie the blood vessel-guided
migration of astrocyte progenitors were inhibited in vivo, the final position of astrocytes in the CP
was affected. Our results demonstrated that astrocyte progenitors in the CP were highly motile andthat the combination of erratic and blood vessel-guided migrations, as well as the mutual dependency
between astrocyte progenitors and blood vessels, facilitated the even and ubiquitous distribution ofastrocytes throughout the CP.

International Symposium on Development and Plasticity of Neural System

S-37

Molecular and functional heterogeneity of neural stem cells
Sebastian Jessberger
Laboratory of Neural Plasticity, Brain Research Institute, Faculties of Medicine and Science,
University of Zurich, 8093 Zurich, Switzerland

Neural stem cells generate new neurons throughout life in distinct regions of the mammalianbrain. This process, called adult neurogenesis, is critically involved in certain forms oflearning and memory. In addition, failing or altered neurogenesis has been associated with anumber of neuro-psychiatric diseases such as major depression and cognitive aging. We aim
to characterize the cellular and molecular mechanisms regulating neural stem cell activity andbehavior on a single cell level. We present new approaches to study the cellular principles
underlying life-long neurogenesis using imaging-based tools and single cell molecularprofiling. Further, we provide evidence for novel molecular mechanisms governing theneurogenic process in the mammalian brain. Thus, the data presented provide new insights
into the cellular principles of hippocampal neurogenesis and identify novel mechanisms
regulating the behavior of rodent and human neural stem cells.

S-38
Novel mechanisms of neurogenesis – the centrosome as a dynamic RNA processing hub
in neurogenesis
Magdalena Götz
Biomedical Center, University of Munich and Institute for Stem Cell Research, Helmholtz Center Munich,Germany

We study the mechanisms of neurogenesis in order to implement them for neuronal repair. I will
briefly summarize our work on a novel centrosomal protein, Akna, that is regulated with great
precision in subsets of neural stem cells and turned off again when young neuroblasts leave thesubventricular zone. This suggested high specificity in centrosome protein association which prompted
us to determine the total proteome of human neural stem cells and neurons derived from humaninduced pluripotent stem cells. Determining the spatial proteome of the centrosome by using 10
different baits that are located at different positions at the centrosome and examining theirreproducible interactors unraveled an unprecedented centrosome heterogeneity in human neural cellswith 60% of all centrosome interactors so far never detected at the centrosome. This is due to the factthat no centrosome proteome of any brain cells had ever been determined and comprised novel hubs ofinteractors related to RNA processing. Strikingly, we observed again a 60% change between thecentrosome proteome from neural stem cells to neurons. revealing and verifying novel diseasecandidates. Analysis of neurodevelopmental disease cohorts identified a significant overrepresentationof NSC, but not neuronal centrosome proteins with variants in patients with periventricular heterotopia(PH). Expressing the PH-associated mutant splicing factor PRPF6 reproduced the periventricularmisplacement in the developing mouse brain, highlighting mis-splicing of transcripts of the MAPkinase SAD-A at centrosomal location as essential for the phenotype. Collectively, cell-type specificcentrosome interactomes explain how genetic variants in ubiquitous proteins may convey brainspecific phenotypes and highlight the yet unappreciated highly dynamic composition of thecentrosome.

International Symposium on Development and Plasticity of Neural System

S-39
Functional rejuvenation of aged neural stem cells by Plagl2 and anti-Dyrk1a activity
Ryoichiro Kageyama
Institute for Frontier Life and Medical Sciences, Kyoto University; RIKEN Center for Brain Science

Regenerative potential of neural stem cells (NSCs) declines during aging, leading to cognitive
dysfunctions. This decline involves up-regulation of senescence-associated genes, but inactivation ofsuch genes failed to reverse aging of hippocampal NSCs. Because many genes are up-regulated or
down-regulated during aging, manipulation of single genes would be insufficient to reverse aging.
Here we searched for a gene combination that can rejuvenate NSCs in the aged mouse brain from
nuclear factors differentially expressed between embryonic and adult NSCs and their modulators. We
found that a combination of inducing the zinc finger transcription factor gene Plagl2 and inhibiting
Dyrk1a, a gene associated with Down syndrome (a genetic disorder known to accelerate aging),
rejuvenated aged hippocampal NSCs, which already lost proliferative and neurogenic potential. Such
rejuvenated NSCs proliferated and produced new neurons continuously at the level observed injuvenile hippocampi, leading to improved cognition. Epigenome, transcriptome, and live imaging
analyses indicated that this gene combination induces up-regulation of embryo-associated genes anddown-regulation of age-associated genes by changing their chromatin accessibility, thereby
rejuvenating aged dormant NSCs to function like juvenile active NSCs. Thus, aging of NSCs can bereversed to induce functional neurogenesis continuously, offering a way to treat age-related
neurological disorders.

International Symposium on Development and Plasticity of Neural System

P-1
Spatial genome organization during neurogenesis
Yuki Fujita
University of Pennsylvania

Gene expression regulated by spatial chromatin organization and nuclear architecture plays crucial rolesin the development of the brain. We have focused on the role of the cohesin complex, which is
chromosome-associated multi-subunit proteins, in embryonic and adult neurogenesis.
Cohesin is a highly conserved nuclear protein complex composed of four subunits, Smc1, Smc3, Scc3,
and Scc1 (Rad21), which form a ring structure.
The cohesin complex is well known for its role in sister chromatid cohesion to maintain the proper cell
cycle process, through its inclusion of the sister chromatid into its ring-like structure. However, thecohesin subunit proteins continue to be expressed in postmitotic cells, including NeuN-positive neurons.
Cohesin mediates chromatin loop formation, which has a role in regulating gene expression. Loss ofcohesin function causes disruptions in chromatin loops, with subsequent effects on transcriptional
regulation.
Mutations that perturb the function of cohesin or the proteins that regulate cohesin function cause
Cornelia de Lange syndrome (CdLS), a rare malformation syndrome characterized by mental
retardation, limb abnormalities, and distinctive facial features. Most of these mutations do not cause
overt defects in cohesion or chromosomal segregation.
To investigate the potential role of cohesin in terminally differentiated cells in vivo, we generated
conditional Smc3-knockout mice. We observed craniofacial abnormality and decreased spine density
in cortical neurons of heterozygous Smc3-knockout mice. Heterozygous Smc3-knockout mice
exhibited increased anxiety-related behavior, which is consistent with a symptom of Cornelia de Lange
syndrome. Thus, neuronal cohesin contributes to neural network formation, and cohesin deficiency
leads to higher brain dysfunction.

International Symposium on Development and Plasticity of Neural System

P-2
Intracellular trafficking of Notch orchestrates temporal dynamics of Notch activity inthe fly brain.
Miaoxing Wang, Makoto Sato
Kanazawa University

Notch signaling is evolutionarily conserved from fly to human and plays diverse biological processes.
Delta acts as a ligand for Notch signaling. It activates Notch receptor only in neighboring cells (transactivation) and autonomously represses Notch activity through the process of cis-inhibition. However,
the molecular mechanism and biological significance of cis-inhibition remain largely elusive. The
wave of differentiation in the Drosophila brain, the ‘proneural wave’, is an excellent model forstudying Notch signaling in vivo. A previous paper in Sato lab showed that Delta expression andNotch activity is upregulated at the wave front of the proneural wave and restricts the speed of wave
propagation. However, Notch is reactivated behind the proneural wave forming the twin peaks ofNotch activity. In this study, we found that strong nonlinearity in cis-inhibition reproduces the second
peak of Notch activity behind the proneural wave in silico. Based on this, we demonstrated that Delta
expression induces a quick degradation of Notch in late endosomes and the formation of the twin
peaks of Notch activity in vivo. Indeed, the amount of Notch was upregulated and the twin peaks werefused forming a single peak when the function of Delta or late endosomes was compromised.
Additionally, we demonstrated that the second Notch peak behind the wavefront controls
neurogenesis. Thus, intracellular trafficking of Notch orchestrates the temporal dynamics of Notch
activity and the temporal patterning of neurogenesis.

International Symposium on Development and Plasticity of Neural System

P-3
The role of PcG in regionalization of the mouse telencephalon
Yusuke Kishi, Hikaru Eto, and Yukiko Gotoh
Graduate School of Pharmaceutical Sciences, The University of Tokyo

During brain development, neural stem-progenitor cells (NPCs) in different brain regions produce
different types of neurons, and each of these regions plays a different role in the adult brain.
Therefore, precise regionalization is essential in the early stages of brain development, and irregularregionalization has been proposed as the cause of neurodevelopmental disorders. The mechanisms
underlying brain regionalization have been well studied in terms of morphogen-induced expression ofcritical transcription factors for regionalization.
We recently revealed that Polycomb group proteins (PcG) play a key role in establishing ventral
identity in the mouse telencephalon. Knockout of Ring1, an essential protein in PcG function, in
neuroepithelial cells induces ectopic expression of dorsal genes, including those for BMP and Wnt
ligands, as well as attenuated expression of the gene for Shh, a key morphogen for ventralization, inthe ventral telencephalon. We performed RNA-seq and epigenomic profiling analyses of NPCs
isolated from each brain region and found the role of PcG in region-specific gene expression in thedeveloping mouse telencephalon.

International Symposium on Development and Plasticity of Neural System

P-4
Mechanical modeling of brain morphogenesis caused by multicellular dynamics
Yoshitaka Kameo1, Hironori Takeda2, Taiji Adachi1
1
2

Kyoto University, Institute for Frontier Life and Medical Sciences, Japan
Kobe University, Graduate School of Engineering, JapanThe cerebrum and cerebellum have convoluted cortexes composed of highly-organized neural layers,which are closely associated with brain functions. The cortical folding is assumed to be mechanicallytriggered by differential growth between cortex and subcortex, where tissue growth and deformation
are caused by cooperative neuronal activities, including proliferation, migration, and axon elongation.
Therefore, to clarify the mechanism of how brains robustly acquire their complex structures andfunctions, comprehensive understanding of the spatiotemporal mechanical behavior of brain tissues
and the underlying multicellular dynamics is of great importance. In this study, we have developed amathematical model of brain morphogenesis that links tissue growth and deformation to cellproliferation and migration. The tissue growth and deformation were formulated based on a theory ofcontinuum mechanics. The cell proliferation and migration were modeled using a balance equation forcell number density, and incorporated into the above tissue model. By utilizing the proposed
mathematical model, we simulated foliation in cerebellar cortex caused by proliferation and migrationof granule cells and investigated the mechanism of folia lengthening. The simulation results showedthat radial migration of granule cells guided by Bergmann glial fibers, whose orientation depends on
the surrounding tissue deformation, is a critical factor to produce elongated folia accompanied by agranule layer with non-uniform thickness. Our mathematical model is a promising framework to
explore the emergence of brain structure and function from mechanical and biochemical viewpoints,
and potentially help clarify the mechanism of various neurological diseases.

Keyword: Brain morphogenesis, Cell proliferation, Cell migration, Mathematical model, Computer
simulation

International Symposium on Development and Plasticity of Neural System

P-5
Development of fluorescent indicators for visualization of N-cadherin interaction across
cells
Tomoki Matsuda
SANKEN (The Institute of Scientific and Industrial Research), Osaka University

For the formation and maintenance of tissues and organs and synaptic transmission, cell adhesion plays
an essential role in multicellular organisms. At the interface of adhering cells, the intercellularinteraction of adhesive molecules attracts adjacent cells. One of the adhesive molecules neural cadherin(N-cadherin) belonging to the classical cadherin family mediates Ca2+-dependent cell adhesions. Ncadherin contributes to a broad range of biological processes, including ontogenesis, cell migration,
neurite outgrowth, and synaptic potentiation. Despite its importance, there is a lack of suitable imaging
techniques to detect these interactions. Therefore, there are difficulties to obtain spatiotemporal
information, when and where N-cadherin interactions occur. To address this situation, we developed
fluorescent indicators to visualize N-cadherin interaction. The indicators are composed of N-cadherin
and dimerization-dependent fluorescent proteins (ddFPs). Through the interaction of N-cadherin
moieties across cells, dimerization of ddFPs, which leads to fluorescence emission, is induced. Our
ddFP based N-cadherin interaction indicators (ddFP-NCad) with reversible property overcome thelimitations of indicators based on the irreversible reconstitution of split fluorescent proteins. We
demonstrated the ability of reversible detection of ddFP-NCad by monitoring the formation anddisruption of N-cadherin interaction through the approach and dissociation of the living cells. We also
successfully visualized N-cadherin interactions in primary neurons and spheroids consisting of multilayered cells. The ddFP-NCad can be applied to a wide range of specimens and could provide useful
insights regarding the spatiotemporal dynamics of N-cadherin interactions in various biologicalprocesses, including the development of the neural system and higher brain functions.

International Symposium on Development and Plasticity of Neural System

P-6
Contractile oscillators regulate the spatial patterning of gut motility
Masafumi Inaba
Kyoto University, Department of Zoology, Graduate School of Science, Kyoto, JapanThe contractile waves on the gut, called peristalsis, play an important role in effective food transportand digestion in many animals. The location where the peristaltic waves emerge is confined at
specific sites of the gut, which enables effective food transport. However, the patterning mechanism
remains to be elucidated. Here, we set up the Ca2+ imaging system (based on GCaMP6s) for theembryonic chicken guts and observed Ca2+ traveling waves that propagate across guts. In the maturegut, Ca2+ waves were associated with the contraction of smooth muscles (SMs). Interestingly, even in
the younger guts which show little muscle contraction, spontaneous Ca2+ waves were observed. The
origins of Ca2+ waves tend to emerge at a specific position which seems to be linked to the initiating
point of peristalsis in the mature gut, therefore the Ca2+ waves we observed here may contribute toestablishing the functional gut movement. Furthermore, we imaged Ca2+ waves likely derived frominterstitial cells of Cajal that function as pacemakers of the peristalsis. In this meeting, we will discuss
how pacemaker waves interact with the spontaneous Ca2+ waves in SMs to achieve functional
peristalsis.

International Symposium on Development and Plasticity of Neural System

P-7
Elucidation of the internal state-dependent modulation of the nociceptive escapebehavior
Tadao Usui
Graduate School of Biostudies, Kyoto University

Adequate behavioral responses to noxious stimuli are essential for organismal survival. Drosophila
larvae exhibit a stereotypic rolling behavior to escape from nociceptive stimuli (e.g., attacks of aparasitoid wasp; Hwang et al., 2007). Although external environmental factors like the wing beat of
the wasps facilitate the escape behavior (Ohyama et al., 2015), little is known about how it can be
modulated by internal states. Here we report that the gene belly roll (bero) negatively regulates thenociceptive escape behavior, and we examine the possibility that a subset of bero-expressing neurons
integrates environmental humidity, a factor influencing body fluid osmolality, into the modulation of
the escape behavior.
We noticed that the magnitude of the escape behavior varies significantly between commonly usedwild-type strains. Prompted by this finding, we performed genome-wide association analyses of thenociceptive responses and identified bero as a candidate gene. We found that bero knockdown larvae
showed enhanced escape behavior upon noxious thermal stimuli. bero is expressed in the multiple
peptidergic interneurons in the larval central nervous system, including the abdominal leucokinin
neuropeptide-producing (ABLK) neurons that respond to nociceptive stimuli and modulate the escapebehavior (Hu et al., 2020). To explore the physiological roles of bero in ABLK neurons, we firstexamined the neural activities of the neurons using Ca2+ imaging. We found that the neurons respond
not only to noxious stimuli but also to extracellular osmolality, and that bero promotes the
hypoosmolality-induced neural activities. Our preliminary data suggest that the hypoosmolalityinduced activity of ABLK neurons inhibit their own nociceptive responses.
Outside of their habitat (e.g., fermenting fruit), Drosophila larvae cannot hide themselves from theparasitoid wasp and are also desiccated, thereby causing hyperosmolality. We discuss the possibility
that the hyperosmolality-dependent facilitation of the escape behavior might promote larval survival.

International Symposium on Development and Plasticity of Neural System

P-8
Thalamocortical axons control the cytoarchitecture of neocortical layers by areaspecific supply of VGFHaruka Sato1, Jun Hatakeyama1, Takuji Iwasato2, Kimi Araki3, Nobuhiko Yamamoto4, Kenji
Shimamura1
1

Department of Brain Morphogenesis, Institute of Molecular Embryology and Genetics, Kumamoto University
Laboratory of Mammalian Neural Circuits, National Institute of Genetics, Japan
3
Division of Developmental Genetics, Institute of Resource Development and Analysis, Kumamoto University
4
Laboratory of Cellular and Molecular Neurobiology, Graduate School of Frontier Biosciences, Osaka
University
2

The adult mammalian neocortex is entirely composed of six layers of neurons, yet the laminarstructure is not uniform throughout the neocortex; the thickness and cellular composition of the layers
differ among cortical areas. For instance, in the sensory cortex, layer 4, which is the main recipientlayer of sensory information from the thalamus, is thick and dense, whereas it is thinner in the motor
area. These features are considered to be crucial for proper functions of the cortical areas, therefore
the developmental mechanisms that regulate the formation of the regionally distinct laminararchitecture has long been a major issue in developmental neurobiology. While some of area-specificfeatures are controlled by intrinsic cues such as morphogens and transcription factors, the exact
influence and mechanisms of action by cues extrinsic to the cortex, in particular the thalamocorticalaxons (TCAs), have not been fully established. Here, we investigated the influence of TCAs on
cortical laminar formation by ablating TCAs from ventrobasal (VB) nucleus at birth. We found thatthe number of layer 4 neurons was decreased in the primary somatosensory area (S1), the target areaof TCAs from VB, during postnatal stages. This was rescued by overexpression of TCA-derived
secreted protein VGF in cortical layer 4 of S1. Furthermore, genetic disruption of Vgf resulted in a
reduction of the layer 4 neuronal number in the sensory areas. Collectively, these results indicated that
TCAs are required for the formation of sensory area-specific laminar structure by regulating thenumber of layer 4 neurons through VGF. Thus, highly site-specific axon projection, which depends on
initial regional patterning of the target fields, in turn contributes to generation of further regional
diversity and complexity within the target tissue.

International Symposium on Development and Plasticity of Neural System

P-9
Neuronal delamination and outer radial glia generation in neocortical development
Ayano Kawaguchi
Department of Anatomy and Cell Biology, Graduate School of Medicine, Nagoya University, Japan

During neocortical development, many neuronally differentiating cells are generated at theapical/ventricular surface by the division of neural progenitor cells (apical radial glial cells, aRG).
Neurogenic cell delamination, in which these neuronally differentiating cells retract their apical
processes and depart from the apical surface, is the first step of their migration. We recently found thatthe microtubule-associated protein Lzts1 is expressed at the AJ of the apical endfeet of the nascentneuronally differentiating cells. It activates actomyosin systems with reduction N-Cadherin localization
at the AJ and induces neuronal delamination. Moreover, we also found that low-level Lzts1 induces theoblique division of aRGs to generate outer radial glia (oRGs)-like cells: oRGs, also called basal radial
glial cells (bRGs), are another type of undifferentiated neural progenitor cell with long radial fibers
extending to the basal side, and their cell body exists in the SVZ, where they divide multiple times.
In addition to neuronal delamination and oblique division, there are various cell departure patterns fromthe apical surface in the developing cerebral wall. Interestingly, these diverse cellular behaviors
appeared in response to the level of overexpressed Lzts1, suggesting that the various cellular departure
events might be understood as a continuous phenomenon linked to common molecular mechanisms,
likely as a spectrum. Our observations further suggest that some neuronal differentiation-related genes,
such as Lzts1, play important roles in cell positioning and histogenesis, even in neural progenitor cells.

International Symposium on Development and Plasticity of Neural System

P-10
A FOXG1-dependent critical period for autism-associated GABAergic circuits
Goichi Miyoshi
Department of Genetic and Behavioral Neuroscience, Gunma University Graduate School of Medicine

Abnormalities in GABAergic inhibitory circuits have been implicated in the etiology of autism
spectrum disorder (ASD). However, when and how defects in inhibitory circuit development can leadto ASD-related social behavioral impairments is unclear. Here, we utilize mouse genetics to determine
how modulation of the ASD-linked gene FoxG1 during specific developmental windows results indysregulated GABAergic circuits and abnormal social behavior. Consistent with both duplication andhaploinsufficiency of FOXG1 observed in syndromic forms of ASD, increased or decreased FoxG1
expression levels result in social impairments in mice but only when alterations take place in both
excitatory and inhibitory populations, indicating a pre-and postsynaptic role for FoxG1 in GABAergic
circuit formation. We observe that the second postnatal week is the critical period for FoxG1
expression to establish juvenile inhibitory circuits and to prevent subsequent ASD social phenotypes.
We further show that transplantation of GABAergic precursor cells prior to this critical periodameliorates the circuit and social behavioral defects of the FoxG1 ASD model, whereas reduction in
GABAergic tone via Gad2 mutation exacerbates them. Our results provide insight into thedevelopmental timing and inhibitory circuit mechanisms that are promising avenues for therapeuticintervention in ASD.

International Symposium on Development and Plasticity of Neural System

P-11
Parallel anatomical connections for song memories between two regions of the zebra
finch higher auditory cortex
Sarah Morson
Okinawa Institute of Science and Technology Graduate University

Male zebra finches learn to sing by listening and memorizing, and then mimicking their tutor’s song
during the developmental critical period. The caudomedial nidopallium (NCM) and caudomedial
mesopallium (CMM) comprise the zebra finch higher auditory cortex. The NCM has been evidenced
as a site of tutor song memories (Yanagihara and Yazaki-Sugiyama 2016), while the neighboring
CMM has been also reported to correlate with memory formation and directly project to the song
motor area, HVC. It has been hypothesized that the NCM and CMM may act as parallel auditory
memory places for tutor song, however the connections between these two regions and how thelocation of tutor song memory may change as birds develop their own song has yet to be understood.
Here, we separately labeled the neurons responding to tutor song and the ones responding to bird’s
own song by using a newly optimized AAV-cFos TetON/TetOFF system (AAV2/9 cFos TetONEGFP and AAV2/9 cFos TetOFF-mRFP) in both the NCM and CMM of adult male zebra finches.
Anatomical analysis has revealed the distinct neuronal populations were activated by either tutorsong, bird’s own song, or both in both the NCM and CMM. The proportions of the tutor song and/or
bird’s own song responsive neurons were not differ between the adult NCM and CMM (n=3 birds,
p>0.05). Our further tracing analysis revealed tutor responsive neurons in the NCM projected to the
CMM and vice versa, suggesting an important interaction between these two regions in storage oftutor song memory.
These suggest that both the NCM and CMM involve neuronal substrates of tutor song memory, andthey are interacting with each other.

International Symposium on Development and Plasticity of Neural System

P-12
The neural basis for overcoming failure: a dopamine circuit facilitates switching toward
new goals
Masaaki Ogawa
Medical Innovation Center / SK project, Graduate School of Medicine, Kyoto University, Kyoto, Japan

How can we eventually achieve our goals despite failures? Humans and animals have the ability tolearn from failures (unsuccessful outcomes), cope with them appropriately, and move forward. This
adaptive ability to overcome failure is a key to achieving a goal, ultimately maximizing the number ofachieved goals. However, the neural basis of the ability is poorly understood. We developed a task inrats to precisely monitor active behavioural switching toward the next reward after failure to obtainreward, based on our previous work (Ogawa M., et al, Neuron, 2013). We then combined this taskwith cell-type-specific recording, dopamine measurement, and circuit-specific optogenetics. We
discovered that a population of dopamine neurons in the ventral tegmental area (VTA) exhibited
increased responses to unexpected failure to obtain reward (no-reward) and decreased responses to
unexpected reward. This bidirectional surprise signal for no-reward was also evident in the dopaminelevel in the nucleus accumbents (NAc). The responses were opposite to and slower than those of thewell-known reward-responsive dopamine neurons important for value-based reward seeking. The
higher the responses to the failure, the faster the switching toward the next reward. The timing of thecorrelation became earlier when no-reward was certain earlier, suggesting that the timing of theswitch was adjusted based on past experience of failure. Further, this correlation appeared even after
the transition to a task in which no-reward could be processed passively, but it gradually weakened.
These findings demonstrate that the dopamine circuitry from the VTA to NAc drives active switching
toward new goals after failure, thereby providing the adaptive ability to overcome failure. As such,the dopamine circuitry, in cooperation with the value-based reward-seeking function, enables robustand efficient achievement of goals.

International Symposium on Development and Plasticity of Neural System

P-13
From Retrospective to Prospective: Integrated Value Representation in Frontal Cortex
for Predictive Choice Behavior
Kosuke Hamaguchi
Department of Biological Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Animals must flexibly estimate the value of their actions (action-value) to successfully adapt to achanging environment. The brain is thought to estimate action-values from two different sources,
namely the action-outcome history (retrospective value) and the knowledge of the environment(prospective value). How and which brain region reconciles these two different estimates of actionvalues to make a choice is not well understood. By combining behavior modeling with reinforcement
learning and two-photon calcium imaging, here we show that as a mouse learns the state-transition
structure of a decision-making task, retrospective and prospective values become jointly encoded in
the preparatory activity of neurons in the anterior lateral motor (ALM) cortex. Suppressing thispreparatory activity in expert mice returned their behavior to a naïve state. These results reveal theneural circuit that integrates knowledge about the past and future to support predictive decisionmaking.

International Symposium on Development and Plasticity of Neural System

P-14
Visual instrumental learning without primary visual cortex
Rikako Kato
Institute for the Advanced Study of Human Biology, Kyoto University, Kyoto, Japan

Blindsight is an ability of visually guided behavior after lesion of the primary visual cortex (V1),despite the loss of visual awareness. The ability of the visual pathways bypassing V1 has been
investigated in various visual functions, but an ability to drive instrumental conditioning has not been
investigated. We used macaque monkeys with unilateral V1 lesion, a model of blindsight, toinvestigate whether visual conditioned stimulus (CS) on the affected visual field by the V1 lesion canplay a role of secondary reinforcer to drive instrumental conditioning. Here, the monkeys wererequired to locate a hidden target area (HA) on a blank monitor in an oculomotor search task. Ifmonkey’s gaze moved to and remained in the HA, the reinforcing visual CS was presented at an edgeof the screen in a location different from the HA. Even when the CS were presented in the affectedvisual field, behavior to locate a HA were promoted. Not only did their gaze get into the HA more
quickly as they learn, but the saccades entering the HA also converged on one or two vectors in eachsession. It indicates that the visual CS acted as secondary reinforcers, reinforcing both the location of
HA and the vector of saccades made immediately before the CS presentation. Reinforcement learningis thought to be driven by the activity of dopamine neurons, which encode reward prediction error
signals. Dopamine neurons of the substantia nigra pars compacta (SNc) in V1 lesion monkeys showedphasic responses to visual CS of hidden target area search task presented in the affected visual field.
These results indicate that the visual inputs via the residual visual pathways after V1 lesions canaccess fundamental neural mechanisms of reinforcement learning.

International Symposium on Development and Plasticity of Neural System

P-15
Regulation of synaptic nanodomain and nanocolumn by liquid–liquid phase separation
Pin-Wu Liu
Graduate School of Science, Nagoya University, Aichi, JapanThe regulation of synaptic glutamate receptors is the basis for memory formation. Observations withsuper-resolution microscopies have revealed an activity dependent reorganization of nanoscalesegregations of glutamate receptors, so called nanodomains, at postsynaptic density (PSD).
Furthermore, postsynaptic nanodomains of glutamate receptors align with presynaptic vesicle
releasing sites to form a trans-synaptic nanocolumn, which regulates the efficacy of synaptictransmission. However, the mechanisms underlying the formation of nanodomain and nanocolumn
remained unclear.
Here we found that calcium/calmodulin-dependent protein kinase II (CaMKII) undergoes liquidliquid phase separation (LLPS) with NMDAR subunit GluN2B through the multivalent interaction
contributed by its dodecameric structure in a calcium-dependent manner. Also, autophosphorylationof CaMKII contributes to maintain this protein condensate by locking CaMKII in an active
conformation. Interestingly, the incorporation of CaMKII into in vitro PSD protein condensate
composed of PSD-95, GluN2B and Stargazin, an auxiliary subunit of AMPAR, resulted in theformation of a core-shell structure, while CaMKII-GluN2B forms shell phase and PSD-95-Stargazin
forms core phase. Furthermore, Neuroligin-1 (NLGN1), a neuronal adhesion molecule, which clusters
with presynaptic neurexin, also segregates together with AMPAR. The segregation of AMPAR and
NMDAR was also observed in living neuron with dual-color direct stochastic optical reconstruction
microscopy (dSTORM). This segregation was disrupted by membrane-permeable CN21 (tat-CN21), a
CaMKII inhibitor, which competes and disrupts CaMKII-GluN2B interaction. In addition, thesegregation between NLGN1 and NMDAR nanodomains was also reduced by tat-CN21.
Taken together, these results suggest that the incorporation of CaMKII into PSD and the interaction
between CaMKII and GluN2B is critical for the formation of AMPAR and NMDAR nanodomains
and the trans-synaptic nanocolumn. Therefore, here we propose that calcium-induced and persistentformation of LLPS by CaMKII, as an activity-dependent crosslinker for postsynaptic proteins, can bea novel mechanism for synaptic plasticity, and serves as molecular basis of memory formation.