sSenri Life Science / WPI-IIIS Joint International Symposium

Sponsored by

Senri Life Science Foundation
International Institute for Integrative Sleep Medicine, University of Tsukuba (WPI-IIIS)
Supported by Biocommunity Kansai (BiocK)

2024 Senri Life Science International Symposium“Science of Behaving and Sleeping Brains”-------- Program ------10:30 - 10:35 Opening address
Shizuo Akira (President of Senri Life Science Foundation)
10:35 - 10:40 Complimentary address
Noriko Osumi (Vice President, Tohoku University)
Chair: Takeshi Sakurai (WPI-IIIS, University of Tsukuba, Japan)
10:40 - 11:25
Talk 1 Deciphering the mysteries of sleep: toward the neuronal substrate for “sleepiness”·· 2

Masashi Yanagisawa (WPI-IIIS, University of Tsukuba, Japan)
11:25 - 12:10
Talk 2 The human SLEEP puzzle: genes, molecules, and circuits
Ying-Hui Fu (University of California San Francisco, USA)12:10 - 13:15································· 6

Lunch

13:15 - 14:00
Talk 3 Neural mechanisms that control hunger ························································· 8
Zachary Knight(Howard Hughes Medical Institute, University of California San Francisco, USA)
Chair: Masashi Yanagisawa (WPI-IIIS, University of Tsukuba, Japan)
14:00 - 14:45
Talk 4 Sleeping Brain: Unveiling the Art of Artificial Induction
Takeshi Sakurai (WPI-IIIS, University of Tsukuba, Japan) ··································· 10
14:45 - 15:00

Coffee break

15:00 - 15:45
Talk 5 Mitochondrial Origins of the Pressure to Sleep
Gero Miesenböck (University of Oxford, UK)··············································· 12
15:45 - 16:30
Talk 6 Making memories in mice
Sheena Josselyn (The Hospital for Sick Children, University of Toronto, Canada) ········ 14
16:30

Closing remarks
Masashi Yanagisawa (WPI-IIIS, University of Tsukuba, Japan)
Described time includes questions and answers.

Introduction
Science of Behaving and Sleeping Brains
Masashi Yanagisawa, MD, PhD
Latest advances in physiological techniques such as neuronal activity imaging/recording andoptogenetic manipulations, combined with cutting-edge molecular genetic tools and single-cellomics, have transformed our investigation into the neurobiology of animal behaviors. We are now
starting to understand how the brain regulates various behaviors in health and disease. Thissymposium will discuss several hot topics of basic behavioral neuroscience in organisms ranging
from flies to mice to humans. Internationally recognized experts in the field will present their latest
work in phenomena ranging from sleeping/waking, hibernating, eating/drinking, to remembering/forgetting.

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Talk 1
Deciphering the mysteries of sleep: toward the neuronalsubstrate for “sleepiness”
Masashi Yanagisawa, MD, PhD
Title:
Director, International Institute for Integrative Sleep Medicine (WPI-IIIS)
University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan
Email: yanagisawa.masa.fu@u.tsukuba.ac.jp / Web: wpi-iiis.tsukuba.ac.jp
Professional membership:
American Academy of Sleep Medicine
Japanese Society of Sleep Research, The Japan Neuroscience Society
Education and Professional Appointments:
1984
MD degree from School of Medicine, Faculty of Medicine, The University of Tokyo1985
M.D. (summa cum laude), 1985, University of Tsukuba
1988
Ph.D. in Medical Sciences, 1988, University of Tsukuba
1988 – 1989
Postdoctoral fellow, Department of Pharmacology, University of Tsukuba
1989 – 1991
Assistant Professor of Pharmacology, University of Tsukuba
1991 – 1991
Assistant Professor of Pharmacology, Kyoto University School of Medicine
1991 – 1996
Associate Professor of Molecular Genetics, University of Texas Southwestern
Medical Center at Dallas (UTSW); Associate Investigator, Howard Hughes
Medical Institute (HHMI)
1996 – 2014
Professor of Molecular Genetics, UTSW; Investigator, HHMI
1998 – 2014
The Patrick E. Haggerty Distinguished Chair in Basic Biomedical Science, UTSW
2001 – 2007
Director, Yanagisawa Orphan Receptor Project (JST/ERATO)
2010 – 2014
Professor and Director, FIRST program, University of Tsukuba
2012 – Present Director, International Institute for Integrative Sleep Medicine (WPI-IIIS),
University of Tsukuba
2014 – Present Adjunct Professor of Molecular Genetics, UTSW
Honors/Awards:
2003
Elected Member, National Academy of Sciences
2016
Medal with Purple Ribbon, Government of Japan2017
Erwin Von Bälz Preis, Boehringer Ingelheim
2018
The Asahi Prize, Asahi Shimbun Foundation
2018
The Keio Medical Science Prize, Keio University Medical Science Fund
2019
Takamine Memorial Daiichi Sankyo Prize, Daiichi Sankyo Foundation of Life Science

2

2019
2022
2023
2023

Person of Cultural Merit, Government of Japan
Toshihiko Tokizane Memorial Award, The Japan Neuroscience Society
Breakthrough Prize in life sciences
Clarivate Citation Laureate

Biographical Narrative:
In 1988, as a graduate student at University of Tsukuba, Yanagisawa discovered endothelin, a potent
vasoconstrictor peptide from vascular endothelial cells, which sparked an intense research activity in thefield. In the subsequent year, his group identified a G protein-coupled receptor for endothelin, which would
become an important drug target; the endothelin receptor antagonist bosentan was approved in 2001 forthe treatment of pulmonary hypertension. After moving to University of Texas Southwestern Medical
Center at Dallas in 1991 as a young principal investigator, he identified the endothelin-converting enzyme,
a metalloprotease that generate the active, mature endothelin peptides. Through gene-targeting experiments
in mice, he also discovered in 1994 that the endothelin pathway is essential for embryonic development ofcertain neural crest derived tissues, and that endothelin-B receptor deficiency causes Hirschsprung diseasein mice and humans. In 1996, he initiated a systematic search for endogenous ligands of “orphan” Gprotein-coupled receptors, which resulted in his 1998 discovery of orexin, a hypothalamic neuropeptide.
He then discovered in 1999 that orexin deficiency causes the sleep disorder narcolepsy. This opened up a
new avenue in sleep research, and led to a better understanding of sleep/wake switching mechanisms in thebrain. The notion that orexin is an important endogenous waking agent led to the development of orexin
receptor antagonists as sleep-inducing drug, first of which, suvorexant, was approved in 2014. Recognizing,
however, that the fundamental mechanism for sleep homeostasis still remains a mystery, in 2010 heembarked upon a highly ambitious project of polysomnography (EEG/EMG)-based forward genetic screen
for sleep/wake abnormalities in chemically mutagenized mouse cohort. This large-scale project is now
continuing in Tsukuba, Japan, and has recently led to identification of several new genes and molecularpathways that are importantly involved in the regulation of sleep amounts and the level of sleep need.

3

Abstract
Although sleep is a ubiquitous behavior in animal species with a nervous system, many aspects
in the neurobiology of sleep remain mysterious. Our discovery of orexin, a hypothalamic
neuropeptide involved in the maintenance of wakefulness, has triggered intensive research
examining the exact role of the orexinergic and other neuronal pathways in the regulation of
sleep/wakefulness. Orexin receptor antagonists, which specifically block the endogenous waking
system, have been approved as a new drug to treat insomnia. Also, since the sleep disordernarcolepsy-cataplexy is caused by orexin deficiency, orexin receptor agonists are expected toprovide mechanistic therapy for the disease; they will likely be also useful for treating excessive
sleepiness due to other etiologies.
Even though the executive neurocircuitry and neurochemistry for sleep/wake switching,including the orexinergic system, has been increasingly revealed in recent years, the mechanism
for homeostatic regulation of sleep, as well as the neural substrate for "sleepiness" (sleep pressure),remains unknown. To crack open this black box, we have initiated a large-scale forward genetic
screen of sleep/wake phenotype in mice based on true somnographic (EEG/EMG) measurements.
We have so far screened >10,000 heterozygous ENU-mutagenized founders and establishedseveral pedigrees exhibiting heritable and specific sleep/wake abnormalities. By combining
linkage analysis and the next-generation whole exome sequencing, we have molecularly identified
and verified the causal mutation in several of these pedigrees. Since these dominant mutations
cause strong phenotypic traits, we expect that the mutated genes will provide new insights into theelusive pathway regulating sleep/wakefulness. Indeed, through a systematic cross-comparison of
the SIK3 Sleepy mutants and sleep-deprived mice, we have found that the cumulative
phosphorylation state of a specific set of mostly synaptic proteins may represent the molecular
substrate of sleep pressure. We have also found that the neuronal molecular pathway LKB1-SIK3HDAC4/5 may represent the level of sleep pressure, regulating the amount, depth, and timing of
sleep by acting in different brain regions, respectively.

4

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Talk 2The human SLEEP puzzle: genes, molecules, and circuits
Ying-Hui Fu, PhD
Title:
Ying-Hui Fu, PhD, Professor of Neurology, University of California San Francisco
Ying-hui.fu@ucsf.edu
Educational Background:1976 - 1980
National Chung-Hsing University, Taichung, Taiwan, B.S., Food Science
1981 - 1986
Ohio State University, Ph.D., Biochemistry & Molecular Biology
1987 - 1989
Ohio State University, Postdoc, Molecular Biology
1990 - 1992
Baylor College of Medicine, Postdoc, Human Genetics
Profesional History:
1993 - 1995
Scientist, Millennium Pharmaceutical Inc., Boston, MA
1995 - 1997
Senior Scientist, Darwin Molecular Corp., Seattle, WA
1997 - 2002
Associate Professor, Department of Neurobiology, University of Utah,
Salt Lake City, UT
2002 - 2006
Associate Professor, Department of Neurology, University of California San
Francisco2006 - Present
Professor, Department of Neurology, University of California San FranciscoAwards and Honors
2006
Sleep Science Award, American Academy of Neurology
2006
Bauer Foundation Colloquium Distinguished Guest, Brandeis University, Boston, MA
2008
Distinguished Guest, Bollum Symposium, University of Minnesota, Minneapolis, MN
2009
Distinguished visiting professorship, Tamkang University, Taiwan
2012
Faculty Research Lecture in Basic Research, UCSF
2012
Presidential Lecture, University of Vermont
2015
TEDx
2018
Member, National Academy of Sciences, USA
2018
Member, Academia Sinica, Taiwan
2018
Member, National Academy of Medicine, USA
2018
Outstanding Alumni Award, Chung-Hsing University, Taiwan
2021
Harvard Medical School Division of Sleep Medicine Prize

6

Abstract
Sleep occupies a significant portion of our daily lives, yet our understanding of sleep, in general, is minimal.
Sleep of sufficient duration, continuity, and intensity is necessary to promote high levels of cognitive
performance during the wake period and prevent physiological changes that may predispose individuals to
many adverse health outcomes. Sleep insufficiency is prevalent in our society due to the high demand forwork, school, and many environmental factors, thus significantly contributing to many health conditions weface. Interestingly, the biological need for sleep varies dramatically among humans. We have identified agroup of humans named “Familial Natural Short Sleep (FNSS)” with unusual sleep behaviors and have usedhuman genetics approach to identify many genes/mutations that give them unusual sleep behaviors. Mouse
models recapitulate the human condition, and in vitro molecular and neurocircuitry studies offer insight into
the underlying mechanisms. Because of sleep's fundamental role in our health, the pathways regulating sleep
are intertwined with those regulating other functions. Thus, our method also offers opportunities toinvestigate how sleep can impact other conditions, including mood, pain, and other disease pathology.
Refernces
1. He Y, Jones CR, Fujiki N, Xu Y, Guo B, Holder J, Nishino S, and Fu Y-H. The transcriptional
repressor DEC2 regulates sleep length in mammals. Science 2009 325:866.
2.

Hirano A, Hsu P-K, Zhang L, Xing L, McMahon T, Yamazaki M, Ptacek LJ, Fu Y-H. DEC2
modulates orexin expression and regulates sleep. Proc Natl Acad Sci USA. 2018 Mar 12.

3.

Shi G, Xing L, Wu D, Jones CR, McMahon T, Chong C, Chen J, Coppola, Geschwind D, Krystal A,
Ptáček LJ, Fu Y-H. A rare mutation of β1-adrenergic receptor affects sleep/wake behaviors. Neuron
2019 Sep 25;103(6):1044-1055.

4.

Webb JM, Ma M, Yin C, Ptacek LJ, Fu Y-H. An Excitatory peri-Tegmental Reticular Nucleus Circuit
for Wake Maintenance. PNAS 2022 July 28. DOI:10.1073/pnas.2203266119.

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Talk 3
Neural mechanisms that control hunger
Zachary Knight, PhD
Department of Physiology, UCSF
Rock Hall, Rm 348F
1550 Fourth St.
San Francisco, CA 94158
415 502 2011zachary.knight@ucsf.edu
Positions2021–Present
2018–Present
2018–2021
2012–2018

Professor, Department of Physiology, UCSF
Investigator, Howard Hughes Medical Institute
Associate Professor, Department of Physiology, UCSF
Assistant Professor, Department of Physiology, UCSF

Education
2006 Ph.D.
1999 B.A.

Chemistry and Chemical Biology. University of California, San Francisco
Chemistry, magna cum laude. Princeton University

Training
2007–2012
2006–2007
2000–2006

Postdoctoral fellow, Rockefeller University. Advisor: Jeff Friedman, M.D. Ph.D.
Postdoctoral fellow, UCSF. Advisor: Kevan M. Shokat, Ph.D.
Graduate student, UCSF. Advisor: Kevan M. Shokat, Ph.D.

Honors and Awards
2019
Presidential Early Career Award for Scientists and Engineers (PECASE)
2018
Investigator, Howard Hughes Medical Institute2016
Helmholtz Young Investigator in Diabetes Award
2016
Pathway Accelerator Award – American Diabetes Association
2015
NIH New Innovator Award
2014
Rita Allen Scholar Award
2014
Alfred P. Sloan Foundation Research Fellow in Neuroscience
2013
New York Stem Cell Foundation – Robertson Neuroscience Investigator Award2013
NARSAD Young Investigator Award
2013
McKnight Technological Innovations in Neuroscience Award
2013
Klingenstein Fellowship Award in the Neurosciences
2013
Program for Breakthrough Biological Research Award - UCSF

8

2009
2007
2006
2002
2001
2000

NIH Pathway to Independence Award
Life Sciences Research Foundation, Postdoctoral Fellowship
UCSF Krevans Distinguished Dissertation AwardGrand Prize Winner, National Collegiate Inventors Competition
Howard Hughes Medical Institute, Predoctoral Fellowship
ARCS Foundation, Predoctoral Fellowship

Abstract
Hunger is controlled by specialized interoceptive neurons that monitor bodily energy stores. How
these cells transform the need for food into the desire to eat is not fully understood. I will describe
our studies investigating the mechanisms that regulate hunger circuits in the forebrain. An
emerging theme is that these circuits integrate sequential sensory cues arising from inside andoutside the body in order to steer the progress of a meal.

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9

Talk 4Sleeping Brain: Unveiling the Art of Artificial Induction
Takeshi Sakurai, MD, PhD
Title:
Professor, Institute of Medicine/WPI-IIIS, University of Tsukuba
EMAIL: sakurai.takeshi.gf@u.tsukuba.ac.jp
Educational Background:1989 Medical Degree
University of Tsukuba, Ibaraki, Japan
1993 PhD (University of Tsukuba)
Professional History:
1993 Postdoctoral fellow of Institute of Basic Medical Sciences
1993Assistant Professor of Institute of Basic Medical Sciences, University of Tsukuba
1995 Postdoctoral fellow HHMI, University of Texas Southwestern Medical Center at Dallas.
1996 Assistant Professor of Institute of Basic Medical Sciences, University of Tsukuba
1999 Associate Professor, Department of Pharmacology,
Institute of Basic Medical Sciences, University of Tsukuba, Japan
2001 Group Leader, Yanagisawa Orphan Receptor Project, Exploratory Researchor Advanced Technology (ERATO), JST

2007
2016 – present

Professor, Department of Molecular Neuroscience and Integrative
physiology, Kanazawa University
Professor, Institute of Medicine/WPI-IIIS, University of Tsukuba

Awards and Honors
2000
Tsukuba Encouragement Prize2009
Ando Momofuku Prize
2012
65th, Chunichi Bunka Award
2013
Prizes for Science and Technology, the Minister of Education, Culture, Sports, Science andTechnology

2018
2020
2021

2nd Shiono Prize
5th Matsuo Prize
32nd Tsukuba Prize10

Abstract
Even when referring to a "sleeping brain," it can exhibit activity in various modes. Sleep encompasses both
REM and non-REM sleep, with several stages of non-REM sleep. Moreover, certain mammals enter ahibernation state as a form of dormancy, serving as a biological strategy for thermoregulating mammals toadapt to harsh environments. What neural circuits facilitate the expression of these various modes of the"sleeping brain"? Recent advancements in neuroscience have uncovered the complexity of the neural circuits
responsible for these switching mechanisms, which are distributed throughout the brain. Additionally,
manipulating these elements has the potential to induce sleep or hibernation states. For example, our group
recently demonstrated the possibility of inducing a hibernation-like state by manipulating a population ofneurons in the hypothalamic preoptic area of mice, a species that typically does not hibernate. We also
showed that initiating REM sleep can be achieved by manipulating dopamine signaling in the amygdala.
These examples illustrate just a few ways in which "sleeping brains" can be induced by manipulating brain
circuits. In the future, manipulating specific neurons in the brain may enable the artificial creation of any
desired state in the sleeping brain.
Refernces
1. Hasegawa E, Miyasaka A, Sakurai K, Cherasse Y, Li Y, Sakurai T. Rapid eye movement sleep is initiated bybasolateral amygdala dopamine signaling in mice. Science. 2022;375(6584):994-1000.

2. Takahashi, T.M., Sunagawa, G.A., Soya, S., Abe, M., Sakurai, K., Ishikawa, K., Yanagisawa, M., Hama, H.,
Hasegawa, E., Miyawaki, A., Sakimura, K., Takahashi, M., Sakurai, T. A discrete neuronal circuit induces ahibernation-like state in rodents, Nature 583, 109–114(2020)・・・・・・・・・・・・・・・ MEMO ・・・・・・・・・・・・・・・・-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

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Talk 5
Mitochondrial Origins of the Pressure to Sleep
Gero Miesenböck, MD
Title:
Waynflete Professor of Physiology
Director, Centre for Neural Circuits and Behaviour
University of Oxford
EMAIL: gero.miesenboeck@cncb.ox.ac.uk
Educational Background:
1993
MD, University of Innsbruck, Austria
1992 – 1998
Postdoctoral Fellow, Memorial Sloan-Kettering Cancer Center
Profesional History:
2011 –
Director, Centre for Neural Circuits and Behaviour, University of Oxford
2007 –
Waynflete Professor of Physiology, University of Oxford
2004 – 2007
Associate Professor of Cell Biology, and of Cellular and Molecular Physiology
Yale University School of Medicine
1999 – 2004
Assistant Member and Head, Laboratory of Neural Systems
Memorial Sloan-Kettering Cancer Center
1999 – 2004
Assistant Professor of Cell Biology and Genetics, and of Neuroscience
Cornell University
Awards and Honors
2023
The Japan Prize
2022
Louisa Gross Horwitz Prize
2020
The Shaw Prize in Life Science and Medicine
2019
Warren Alpert Foundation Prize
2016
The Massry Prize
2016
Member, German Academy of Sciences Leopoldina
2015
BBVA Foundation Frontiers of Knowledge Award in Biomedicine
2015
Fellow of the Royal Society
2015
Heinrich Wieland Prize
2014
Member, Austrian Academy of Sciences
2013
Gabbay Award in Biotechnology and Medicine
2013
The Brain Prize
2012
InBev-Baillet Latour International Health Prize

12

Abstract
The essential but enigmatic functions of sleep must be reflected in physical changes sensed by thebrain's sleep-control systems. In Drosophila, a handful of sleep-inducing neurons projecting to thedorsal layers of the fan-shaped body (dFBNs) estimate sleep pressure by monitoring the flow ofelectrons through their own mitochondria. Sleep loss diverts high-energy electrons from therespiratory chain into uncontrolled side reactions with molecular oxygen, producing reactive
oxygen species which fragment the polyunsaturated fatty acyl (PUFA) chains of membrane lipids
into short- or medium-chain carbonyls. dFBNs transduce this biochemical signal into sleep in aprocess that involves an allosteric dialogue between the voltage sensors of the potassium channel
Shaker—a critical determinant of dFBN activity—and the active sites of its redox-sensitive βsubunit Hyperkinetic. The oxidation state of Hyperkinetic's nicotinamide adenine dinucleotide
phosphate (NADPH) cofactor changes when PUFA-derived carbonyls abstract an electron pair.
NADP+ remains locked in the active site of KVβ until membrane depolarization permits its release
and replacement with NADPH. dFBNs use this voltage-gated oxidoreductase cycle to encode theirrecent lipid peroxidation history in the collective binary states of their KVβ-subunits; thisbiochemical memory influences—and is erased by—spike discharges driving sleep. The presenceof a lipid peroxidation sensor at the core of homeostatic sleep control suggests that sleep protects
neuronal membranes against oxidative damage. Sleep, like ageing, may thus be a consequence of
aerobic metabolism.

References
1. Donlea, J.M., Pimentel, D., and Miesenböck, G. (2014) Neuronal machinery of sleep homeostasis in
Drosophila. Neuron 81: 860–872.
2. Pimentel, D., Donlea, J.M., Talbot, C.B., Song, S.M., Thurston, A.J.F., and Miesenböck, G. (2016)
Operation of a homeostatic sleep switch. Nature 536: 333–337.
3. Kempf, A., Song, S.M., Talbot, C.B., and Miesenböck, G. (2019) A potassium channel β-subunit
couples mitochondrial electron transport to sleep. Nature 568: 230–234.

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Talk 6Making memories in mice
Sheena Josselyn, PhD
Title:
Professor, University of Toronto
Senior Scientist, Hospital for Sick Children (Research Institute)
EMAIL: sheena.josselyn@sickkids.ca
Educational Background:1996 PhD (Psychology, Neuroscience)
University of Toronto, Toronto, Canada
1991 MA (Clinical Psychology)
Queen’s University at Kingston, Canada
1989 BA (Psychology)
Queen’s University at Kingston, Canada
1987 BScH (Life Sciences)
Queen’s University at Kingston, Canada
Professional History:
2003 - Present Senior Scientist, Hospital for Sick Children, Toronto, Canada
2003 - Present Professor, University of Toronto, Toronto, Canada
1998 - 2003
Research Associate, UCLA, Los Angeles, California, USA
1997 - 1998
Post-doctoral Fellow, Yale University, Ct, USA
1996 - 1997
Post-doctoral Fellow, Clarke Institute of Psychiatry (now CAMH), Toronto, CanadaAwards and Honors
2023
The Betty & David Koester Award for Brain Research (University of Zurich)
2022
National Academy of Medicine US
2022
Hughlings Jackson Award Lecturer (McGill)
2021
Andrew Carnegie Prize in Mind and Brain Sciences
2021
Benning Society Lecturer (University of Utah School of Medicine)2021
Blum Lecturer (UT San Antonio)
2019
UCLA Distinguished Lecture Award2018
Fellow, Royal Society of Canada (Life Sciences Division)
2018
Pavlovian Society Research Award
2017
Senior Fellow, Massey College (University of Toronto)
2016 - 2021
Senior Fellow, Canadian Institute for Advanced Research (CIFAR)
2016
Brenda Milner Lecturer (University of Lethbridge)

14

2016
2016-2023
2014
2012
2009-20142009
2008-2011

Bryan Kolb Lecture in Behavioural Neuroscience (University of Calgary)
Canada Research Chair (CRC) in Brain and Cognition Tier I
Daniel H. Efron Research Award, American College of Neuropsychopharmacology(ACNP)
Travel award from American College of Neuropsychopharmacology (ACNP)
Canada Research Chair (CRC) in Molecular and Cellular Cognition Tier II (renewal)
Innovations in Psychopharmacology Award, Canadian College of
Neuropsychopharmacology (CCNP)EJLB Scholar

15

Abstract
Understanding how the brain uses information is a fundamental goal of neuroscience. Several
human disorders (ranging from autism spectrum disorder to PTSD to Alzheimer’s disease) may
stem from disrupted information processing. Therefore, this basic knowledge is not only criticalfor understanding normal brain function, but also vital for the development of new treatment
strategies for these disorders. Memory may be defined as the retention over time of internal
representations gained through experience, and the capacity to reconstruct these representations atlater times. Long-lasting physical brain changes (‘engrams’) are thought to encode these internal
representations. The concept of a physical memory trace likely originated in ancient Greece,
although it wasn’t until 1904 that Richard Semon first coined the term ‘engram’ (Semon, 1904).
Despite its long history, finding a specific engram has been challenging, likely because an engram
is encoded at multiple levels (epigenetic, synaptic, cell assembly). My lab is interested inunderstanding how specific neurons are recruited or allocated to an engram (Han et al., 2007; 2009),
and how neuronal membership in an engram may change over time or with new experience (Rashid
et al., 2016; Josselyn & Tonegawa, 2020). Here I will describe data in our efforts to understandmemories in mice.

Refernces
1. R. Semon, Die Mneme als erhaltendes Prinzip im Wechsel des organischen Geschehens. W.
Engelmann, Ed., (Leipzig, 1904).
2. Han JH, Kushner SA, Yiu AP, Hsiang HL, Buch T, Waisman A, Bontempi B, Neve RL,Frankland PW, Josselyn SA (2009). Selective erasure of a fear memory. Science, 323,
1492-1496.
3. Han JH, Kushner SA, Yiu AP, Cole CA, Matynia A, Brown RA, Neve R, Guzowski JF,
Silva AJ, Josselyn SA (2007). Neuronal competition and selection during memory
formation. Science, 316, 457-460.
4. Rashid AS, Yan C, Mercaldo V, Hsiang HW, Park S, Cole CJ, De Cristofaro A, Yu J,
Ramakrishnan C, Lee SY, Deisseroth K, Frankland PW*, Josselyn SA* (2016).
Competition between engrams influences fear memory formation and recall. Science, 353,
383-7.
5. Josselyn SA & Tonegawa S (2020). Memory engrams: Recalling the past and imagining thefuture. Science, 367, 6473-6480.

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17

Evacuation routes of the 5th floor

Evacuation routes on the 1st floor There is an announce in an emergency. We will provide guidance if
evacuation becomes necessary. Please remain at your seat, stay calm,
and await instructions from the staff.
 During evacuation, please exit the route indicated by the red arrows.
 Don’t use the elevators.

Senri Life Science Foundation
Level 20, Senri Life Science Center Building
1-4-2, Shinsenri-Higashimachi, Toyonaka-City,
Osaka 560-0082, Japan
Phone: 06-6873-2006, Fax: 06-6873-2002
E-mail: smp-2022@senri-life.or.jp
URL: https://www.senri-life.or.jp