OMB No. 0925-0001 and 0925-0002 (Rev. 10/2021 Approved Through 01/31/2026)

BIOGRAPHICAL SKETCH
Provide the following information for the Senior/key personnel and other significant contributors.
Follow this format for each person. DO NOT EXCEED FIVE PAGES.

NAME: Kei M. Igarashi, Ph.D.
eRA COMMONS USER NAME (credential, e.g., agency login): KIGARASHIPOSITION TITLE: Associate Professor
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing,include postdoctoral training and residency training if applicable. Add/delete rows as necessary.)
DEGREE(ifapplicable)

Completion
Date
MM/YYYY

University of TokyoBS

03/2001

Molecular Biology

University of Tokyo

PhD

03/2007

Neurophysiology

University of Tokyo

Postdoc

04/2009

Neurophysiology

Norwegian University of Science and Technology

Postdoc

12/2015

Systems Neuroscience

INSTITUTION AND LOCATIONFIELD OF STUDY

A. Personal Statement
Throughout my career, a central direction of my research has been to understand how interactions between
multiple brain regions give rise to behavior and how impairment of these interactions results in disease. To thisend, I have been pursuing research using the entorhinal-hippocampal circuit as a model system, andinvestigating cellular and circuit mechanisms that support memory. I have a broad background in systems
neuroscience, with extensive training in functional optical imaging (Igarashi & Mori, J Neurophys, 2005) andsingle-cell neuroanatomy (Igarashi et al., J Neurosci 2012) during my PhD with Kensaku Mori at the Universityof Tokyo, and in high-density electrophysiology from rodents performing memory tasks and spike/local fieldpotential (LFP) analyses (Igarashi et al., Nature 2014) during my postdoc research in the lab of Edvard Moserand May-Britt Moser at the Norwegian University of Science and Technology. In my lab at the University ofCalifornia, Irvine (UCI), we investigate (1) cellular and circuit mechanisms of associative memory in healthy
subjects (Lee et al., Nature 2021), and (2) how impairments of memory circuit mechanisms cause memory
deficit in Alzheimer’s disease (Jun et al., Neuron 2020).

1. Jun H, Lee JY, Bleza, N, Ichii A, Donohue JD, and Igarashi KM* (2024)
Prefrontal and lateral entorhinal neurons co-dependently learn item-outcome rules.
Nature, doi: 10.1038/s41586-024-07868-1
2. Lee JY, Jun H, Soma S, Nakazono T, Shiraiwa K, Dasgupta A, Nakagawa T, Xie JL, Chavez J,Romo R, Yungblut Y, Hagihara M, Murata K, and Igarashi KM* (2021)
Dopamine facilitates associative memory encoding in the entorhinal cortex.
Nature 598: 321-326 PMID: 34552245
3. Jun H, Soma S, Saito T, Saido TC, Igarashi KM* (2020)
Disrupted place cell remapping and impaired grid cells in a knock-in model of Alzheimer’s disease
Neuron 107:1095-1112 PMID: 32697942
4. Igarashi KM*, Lu L, Colgin LL, Moser MB, Moser EI* (2014)
Coordination of entorhinal-hippocampal ensemble activity during associative learning.
Nature 510: 143-7 PMID: 24739966 (*Co-corresponding authors)

B. Positions, Scientific Appointments, and Honors
Positions and Employment
2023-present
Chancellor’s Fellow, UC Irvine
2022-present
Associate Professor (tenured);
2016- 2022 Assistant Professor,
Department of Anatomy & Neurobiology, UC Irvine
2016-present
Fellow, Center for the Neurobiology of Learning & Memory, UC Irvine
2018-present
Faculty Member, Institute for Memory Impairments and Neurological Disorders, UC Irvine
2009-2015
Postdoctoral Fellow/Research Associate with Drs. Edvard Moser and May-Britt Moser,
Kavli Institute for Systems Neuroscience, Norwegian University of Science and Technology
2007-2009
Postdoctoral Fellow with Drs. Kensaku Mori and Manabu Tanifuji
University of Tokyo School of Medicine/RIKEN Brain Science Institute2008
Visiting Researcher with Drs. Wei R Chen and Gordon Shepherd, Yale University
2003-2007
PhD student with Dr. Kensaku Mori, University of Tokyo School of Medicine
2001-2003
MS student with Dr. Kensaku Mori, University of Tokyo School of Medicine
2000-2001
Undergraduate research assistant with Dr. Hitoshi Sakano, University of Tokyo
Scientific Appointments
2024
NIH Chronic Dysfunction and Integrative Neurodegeneration (CDIN) study section, Ad-hocreviewer
2023
External Review Member, Pasteur Institute, France
2022-present
Society for Neuroscience, Diversity and Inclusion Working Group2022-present
Society for Neuroscience, Program Committee
2020-present
Japan Neuroscience Society, Diversity Committee
2019-present
Japan Neuroscience Society, International Collaboration Affairs Committee
2022, 2023
NIH Learning, Memory and Decision Neuroscience (LMDN) study section, Ad-hoc reviewer
2022, 2023
European Research Council (ERC), Ad-hoc reviewer
2022
NIH Special Emphasis study section on Alzheimer’s disease research (ZRG1 IFCN-J 02),Ad-hoc reviewer
2020
NIH Brain Initiative study section (ZRG1 IFCN-T(55)), Ad-hoc reviewer
2020
Wellcome Trust (UK), Ad-hoc reviewer
2019, 2022
Israel Science Foundation, Ad-hoc reviewer
2019, 2020
NIH Neurobiology of Learning and Memory (LAM) study section, Ad-hoc reviewer
2019
Alzheimer’s Research United Kingdom, Ad-hoc reviewer
2017 – present
Alzheimer’s Association, standing grant reviewer
Member: Cajal Club (2019 – ), Federation of European Neuroscience Societies (2010 – ), NorwegianNeuroscience Society (2010 – ), Society for Neuroscience (2005 – ), Japan Neuroscience Society (2001 – )Reviewer for Journals: Nature, Science, Cell, Nat Neurosci, Neuron, Sci Adv, Mol Psych, J Neurosci, eLife,
Frontier journals, Cell Reports, Scientific Reports, PLoS Biology, J Neurophysiol, Curr Opin Neurobiol
Honors
2023
2023
2023
2022, 2023
2022
2022
2019
2019
2018
2017
2016
2016
2014
2013
2012
2007 – 20092004 – 2007

Japan Academy Medal
Japan Society for Promotion of Science (JSPS) Prize
Silver Beaker Award for Excellence in Teaching, UC Irvine School of Medicine
Medical Education Excellence Award in Teaching, UC Irvine School of Medicine
Robert & Sylvia Mapel Research Endowment, UC Irvine School of Medicine
Outstanding Early-Career Faculty Research Award, UC Irvine School of Medicine
Alzheimer’s Disease Research Award, BrightFocus Foundation
New Vision Award for Alzheimer’s Disease Research, Donors Cure Foundation
Ando Momofuku Award, Ando Foundation
Mishima Kaiun Prize, Mishima Kaiun Memorial Foundation
Fay/Frank Seed Grant, Brain Research Foundation
PRESTO Career Development Award, Japan Science and Technology Agency
Young Investigator Award, Japan Neuroscience Society
Gordon Research Conference Travel Award
Norwegian Research Council Postdoctoral Fellowship
Postdoctoral Fellowship, Japan Society for the Promotion of SciencePredoctoral Fellowship, Japan Society for the Promotion of ScienceC. Contributions to Science
1. In the current learning and memory research, one of the most important and outstanding questions is tounderstand circuit mechanisms underlying associative memory, which is the most common form ofmemory in our daily life. In the past 30 years, neuronal circuits underlying spatial memory and navigation
have been identified by O’Keefe, Moser, and Moser (2014 Nobel Prize). Despite these findings, mechanisms
for episodic memory remain unclear. During my postdoc, I showed that the lateral entorhinal cortex (LEC)
plays a major role in associative memory (Igarashi et al., Nature 2014). To summarize the function of theentorhinal cortex, I wrote a review paper (Igarashi, Brain Res, 2016). However, my previous study was acorrelational recording study of LEC spike activities from rats. This type of correlational recording study has
been from the classical tradition in electrophysiology research over the decades, and subsequentcorrelational recording studies from other labs further implicated roles of the LEC in various functions. Ourviews on the function of the LEC have thus been significantly divided in the past 10 years, hampering
advancement of the field. A major reason for this discordance was that these studies, including ours, weremerely correlational, without any circuit interventions, and recordings were collected from unknown neuronalpopulations. Since I started my lab, I have investigated the role of the LEC using cell-type-specificintervention and recording to challenge the status quo in the field. After a long-term effort, we recentlyobtained compelling results demonstrating that neurons in the LEC play a critical role in associative memory,a fast-type associative learning between newly-learned information and pre-learned memory (Lee, Jun etal., Nature, 2021). We also found that dopamine input to the LEC plays a critical role in associative memory.
Our results provide a breakthrough in the field of learning and memory research, demonstrating that the LEC
is the brain area that achieves associative memory. Furthermore, our novel discovery about how dopamine
controls the LEC will bring a major conceptual breakthrough in that two previously independent fields ofneuroscience, memory research and reinforcement learning, can be now unified.
a. Jun H, Lee JY, Bleza, N, Ichii A, Donohue JD, and Igarashi KM* (2024)
Prefrontal and lateral entorhinal neurons co-dependently learn item-outcome rules.
Nature, doi: 10.1038/s41586-024-07868-1
b. Igarashi KM*, Lee JY, Jun H (2022) Reconciling neuronal representations of schema, abstract task
structure, and categorization under cognitive maps in the entorhinal-hippocampal-frontal circuits
Curr Opin Neurobiol 77:102641 PMID: 36219950
c. Lee JY, Jun H, Soma S, Nakazono T, Shiraiwa K, Dasgupta A, Nakagawa T, Xie JL, Chavez J, Romo R,Yungblut Y, Hagihara M, Murata K, and Igarashi KM* (2021) Dopamine facilitates associative memory
encoding in the entorhinal cortex. Nature 598: 321-326 PMID: 34552245
d. Igarashi KM*, Lu L, Colgin LL, Moser MB, Moser EI* (2014). Coordination of entorhinal-hippocampal
ensemble activity during associative learning. Nature 510: 143-7 PMID: 24739966
2. Alzheimer's disease (AD) currently affects 50 million people worldwide, but no cure exists. Although previous
studies are shedding light on molecular and cellular mechanisms of AD, it remains unclear what type ofimpairment in neuronal activity causes memory impairment in AD subjects. This is a critical gap in knowledge
in current AD research: If we can clearly identify such mechanisms, we may be able to develop a therapeutic
treatment to prevent the deterioration of memory circuits in AD patients. To fill this critical gap, I have been
striving to elucidate circuit mechanisms of AD that cause memory impairment using in vivo circuit analysis
and electrophysiological methods applied to a mouse model of AD. My specific focus is the role of theentorhinal cortex in AD pathogenesis. Although it has long been known that the entorhinal cortex is theprimary brain area showing functional and cellular degeneration in the early phase of AD, little has been
known about the entorhinal cortex in AD because AD research has emphasized the hippocampus. We first
focused on gamma oscillations, a network activity essential for the communication between the entorhinal
cortex and hippocampus. We provided the first evidence that in vivo gamma oscillations are impaired in theentorhinal cortex of an AD mouse model (Nakazono et al., Front Syst Neurosci, 2017). This finding wasalso summarized in our review (Nakazono et al., Neurosci Res, 2018). To determine what circuit activity iscausing memory impairment, we recently provided the first evidence that the impairment of place cellremapping, a network activity for distinguishing different environments, is disrupted in an AD mouse model(Jun et al., Neuron 2020). We showed that the remapping deficit emerges together with memory impairment
over the course of pathogenesis, whereas the impairment of grid cells in the entorhinal cortex precedes theremapping/memory impairment. Our results suggest that remapping impairment is a circuit mechanism
underlying spatial memory impairment in AD, and grid cell degeneration can be a primary cause of remappingimpairment in the hippocampus. Our finding is expected to lead to future therapeutic methods that slow therate of spatial memory decline in AD patients. Since the publication of the Neuron paper we have received
an increasing number of requests to provide experimental methods. To share the methods with a larger
community, we published a protocol paper (Jun et al., STAR Protocols, 2021). Recently we further showedthat sharp-wave ripples are impaired in our AD mouse model (Funane et al., Front Syst Neurosci, 2022). I
recently reviewed current knowledge about activity dysfunctions of the entorhinal cortex (Igarashi, Trends
Neurosci, 2023).
a. Igarashi KM* (2023)
Entorhinal cortex dysfunction in Alzheimer's disease
Trends in Neuroscience, 46: 124-136 PMID: 36513524b. Funane, T, Jun H, Sutoko, S, Saido TC, Kandori A, and Igarashi KM* (2022) Impaired sharp-wave ripple
coordination between the medial entorhinal cortex and hippocampal CA1 of knock-in model ofAlzheimer’s Disease. Front Syst Neurosci 16:955178 PMID: 36090186
c. Jun H, Soma S, Saito T, Saido TC, Igarashi KM* (2020) Disrupted place cell remapping and impaired
grid cells in a knock-in model of Alzheimer’s disease Neuron 107:1095-1112 PMID: 32697942
d. Nakazono T, Lam TN, Patel AY, Kitazawa M, Saito T, Saido TC, Igarashi KM* (2017). Impaired In Vivo
Gamma Oscillations in the Medial Entorhinal Cortex of Knock-in Alzheimer Model. Front Syst Neurosci
11:48 PMID: 28713250
3. During my postdoctoral work in the Moser lab, I also investigated pattern separation of place cells andgrid cells in the hippocampus and medial entorhinal cortex during animals’ spatial memory. We found thatplace cells in the CA2 area of the hippocampus show pattern completion (memory filling-in) compared tothose in CA3, which showed pattern separation (memory dissociation). I also investigated the roles of gamma
oscillations in the spatial representation of grid cells in the medial entorhinal cortex (paper in preparation).
a. Igarashi KM* (2016). Entorhinal map of space. Brain Research 1637:177-87. PMID: 26940561
b. Lu L, Igarashi KM, Witter MP, Moser EI, Moser MB (2015). Topography of Place Maps along the CA3to-CA2 Axis of the Hippocampus. Neuron 87:1078-92. PMID: 26298277
4. My Ph.D. and successive short postdoc works identified olfactory brain circuits that enable rodents toprocess a wide variety of odor information. These studies were performed in the laboratory of Kensaku Moriat the University of Tokyo. Basic circuitry in the olfactory brain regions, including the olfactory bulb andolfactory cortex, has been long unexplored, and thus it was unclear how the brain processes odor information.
I have investigated rodent olfactory circuits, as they share olfactory brain regions of a similar structure tothose in humans. In the publications listed below, I used a variety of imaging, electrophysiology, andanatomical techniques to investigate the circuit architecture of the olfactory bulb and cortex. I found that asmall, compartmentalized structure in the olfactory bulb (glomeruli) processes information of distinct odor
molecules, forming clusters for hydrophilic and hydrophobic odors. I further discovered that individual odor
information is decomposed into temporally fast coarse information and slow precise information by two
distinct cell types, and conveyed to distinct regions in the olfactory cortex. These results contributed to thefoundations of current research on olfactory perception and behaviors, and have been cited as backgroundreferences in many research papers. I continue working with my long-term collaborators to understand circuitmechanisms for olfactory sensory processing.
a. Cavarretta F, Burton SD, Igarashi KM, Shepherd GM, Hines ML, Migliore M (2018) Parallel odor
processing by mitral and middle tufted cells in the olfactory bulb. Scientific Reports 8:7625 PMID:29769664
b. Igarashi KM*, Ieki N, An M, Yamaguchi Y, Nagayama S, Kobayakawa K, Kobayakawa R, Tanifuji M,Sakano H, Chen WR, Mori K.* (2012). Parallel mitral and tufted cell pathways route distinct odor
information to different targets in the olfactory cortex. Journal of Neuroscience 32:7970-85 (*Cocorresponding authors) PMCID: PMC3636718
c. Mori K, Takahashi YK, Igarashi KM, Yamaguchi M. (2006). Maps of odorant molecular features in theMammalian olfactory bulb. Physiol Rev 86:409-433 PMID: 16601265
d. Igarashi KM, Mori K. (2005). Spatial representation of hydrocarbon odorants in the ventrolateral zonesof the rat olfactory bulb. Journal of Neurophysiology 93:1007-1019 PMID: 15385587

Complete list of published work can be found on PubMed
https://pubmed.ncbi.nlm.nih.gov/?term=Igarashi+KM%5Bau%5D&sort=date