Search Results for: kei igarashi

Kei Igarashi

Imagine that you smell some delicious foods as you walk down a street – and suddenly you start to recall the good old days you had that dish when you were small. This is a typical example showing the powerful link between memory and olfaction – the sense of smell. But how do neuronal circuits in your brain enable that? And why do we have to loose such a precious memory when we get old?

My lab is investigating circuit mechanism of sensory perception and memory, using rodents as model organisms. We are also clarifying what neural circuits are affected and how the impairments of neuronal activities cause memory loss in Alzheimer’s disease.

 

 

Lab Website


Publications

Impaired In Vivo Gamma Oscillations in the Medial Entorhinal Cortex of Knock-in Alzheimer Model
Nakazono T, Lam TN, Patel AY, Kitazawa M, Saito T, Saido TC, Igarashi KM*
Front Syst Neurosci,  11:48 (2017)

Entorhinal map of space
Igarashi KM* (*Corresponding author)
Brain Research,  1637:177-187 (2016)

Topography of Place Maps along the CA3-to-CA2 Axis of the Hippocampus.
Lu L, Igarashi KM, Witter MP, Moser EI, Moser MB.
Neuron. 87:1078-92 (2015)

Plasticity in oscillatory coupling between hippocampus and cortex
Igarashi KM* (*Corresponding author)
Curr Opin Neurobiol. 35:163-168 (2015)

Coordination of entorhinal-hippocampal ensemble activity during associative learning.
Igarashi KM*, Lu L, Colgin LL, Moser MB, Moser EI* (*Co-corresponding authors)
Nature. 510: 143-7 (2014)

Functional diversity along the transverse axis of hippocampal area CA1.
Igarashi KM*, Ito HT, Moser EI, Moser, M-B. (*Corresponding author)
FEBS Lett. 588:2470-2476 (2014)

Parallel mitral and tufted cell pathways route distinct odor information to different targets in the olfactory cortex.
Igarashi KM*, Ieki N, An M, Yamaguchi Y, Nagayama S, Kobayakawa K, Kobayakawa R, Tanifuji M, Sakano H, Chen WR, Mori K*  (*Co-corresponding authors)
Journal of Neuroscience. 32:7970-85 (2012)

Genetic visualization of the secondary olfactory pathway in Tbx21 transgenic mice.
Mitsui S, Igarashi KM, Mori K and Yoshihara Y
Neural Systems & Circuits. 1:5 (2011)

Swept source optical coherence tomography as a tool for real time visualization and localization of electrodes used in electrophysiological studies of brain in vivo.
Watanabe H, Rajagopalan UM, Nakamichi Y, Igarashi KM, Kadono H, Tanifuji M.
Biomedical Optics Express. 2:3129-3134 (2011)

In vivo layer visualization of rat olfactory bulb by a swept source optical coherence tomography and its confirmation through electrocoagulation and anatomy.
Watanabe H, Rajagopalan UM, Nakamichi Y, Igarashi KM, Madjarova VD, Kadono H, Tanifuji M.
Biomedical Optics Express. 2:2279-2287 (2011)

Two highly homologous mouse odorant receptors encoded by tandemly-linked MOR29A and MOR29B genes respond differently to phenyl ethers.Tsuboi A, Imai T, Kato HK, Matsumoto H, Igarashi KM, Suzuki M, Mori K, Sakano H.
European Journal of Neuroscience. 33:205-13 (2011)

Differential axonal projection of mitral and tufted cells in the mouse main olfactory system.
Nagayama S, Enerva A, Fletcher ML, Masurkar AV, Igarashi KM, Mori K, Chen WR.
Frontiers in Neural Circuits. 4. Pii120 (2010)

Dendrodendritic synapses and functional compartmentalization in the olfactory bulb.
Mori K, Matsumoto H, Tsuno Y, Igarashi KM.
Ann N Y Acad Sci. 1070:255-258 (2009)

Maps of odorant molecular features in the Mammalian olfactory bulb.
Mori K, Takahashi YK, Igarashi KM, Yamaguchi M.
Physiol Rev. 86:409-433 (2006)

Spatial representation of hydrocarbon odorants in the ventrolateral zones of the rat olfactory bulb.
Igarashi KM, Mori K.
Journal of Neurophysiology. 93:1007-1019 (2005)

Odor Maps in the Dorsal and Lateral Surfaces of the Rat Olfactory Bulb.
Mori K, Takahashi YK, Igarashi K, and Nagayama S
Chemical Senses30:i103-i104 (2005)

Navigating brain oscillations and Alzheimer’s disease

Space, the final frontier. Uncharted and unexplored, it remains a mystery to us. But aside from the common cliché – apologies to all Trekkies – space is much more than the enigmatic celestial void we contemplate with wonder and awe. It is everything around us, from our personal space to traversing the planet. Navigating successfully around space is essential to our survival as a species. Some may be better than others. There’s even a gender difference, but I’ll let you guess what it is. As we get older, all of us begin to struggle a little with navigating around new as well as familiar spaces. But for a patient with Alzheimer’s disease, this ability can be severely compromised. Enter Kei Igarashi, assistant professor of Anatomy and Neurobiology and Fellow of the Center for the Neurobiology of Learning and Memory (CNLM) at the University of California, Irvine. His work is making strides in understanding how spatial navigation and spatial memory mechanisms deteriorate in Alzheimer’s disease, potentially paving the way to improved diagnosis and treatment.

I arrived at Igarashi’s newly established lab in Irvine Hall on the medical school campus ready to pepper him with questions about his most recent paper. He welcomed me into his no frills office looking out onto Irvine’s expanse of undeveloped desert.

On one side stood a wooden chair etched with the University of California letters. “I bought this for 30 bucks!” he commented with pride. On the other side stood a bookcase where one book in particular was placed prominently in front – a pristine copy of The Cognitive Neuroscience of Memory by Howard Eichenbaum, a memory pioneer who had passed away suddenly only a few days before our interview. Eichenbaum visited the Irvine CNLM just a few months before and Igarashi made sure to get his copy of the book signed by the distinguished author. “His early studies on olfaction informed my work a great deal. Such a tragic loss to us all…” he soberly remarked.

Kei Igarashi with 2014 Nobel Laureates Edvard and May-Britt Moser and John O’Keefe

He asked me to sit down on a cushioned chair next to his desk, as I pulled out my camera, pen, and notepad. Igarashi arrived at Irvine in the spring of 2016 after completing a highly coveted postdoctoral fellowship with Edvard and May-Britt Moser. The Mosers were awarded the 2014 Nobel Prize in Physiology or Medicine, an award they shared with University College London’s John O’Keefe for their collective discoveries related to the brain mechanisms of spatial navigation. The Mosers direct the Kavli Institute for Systems Neuroscience in Trondheim, Norway. “I could not have asked for better mentors in fundamental science”, he said.

Since arriving at Irvine, Igarashi’s lab has focused on making new inroads into understanding the role of brain oscillations in spatial processing and how these mechanisms are disrupted in Alzheimer’s disease. Spatial navigation involves a set of interconnected circuits nestled in regions deep in the brain, the hippocampus and the entorhinal cortex. The same two regions are among the earliest sites to deteriorate in Alzheimer’s. A coincidence? Likely not. Igarashi is studying this intricate system in detail to identify why it fails.

His lab is recording electrical activity directly from these regions in a novel Alzheimer’s mouse model. The amyloid precursor protein (APP) knock-in model developed by Japanese researchers in 2014, he explained, offers several advantages over transgenic models. This particular model exhibits typical age-related pathology without overproduction of other APP fragments. His findings, published in June of this year, show impairments in the synchrony or coupling of brain waves in these mice. In the normal brain, two different types of brain waves (gamma and theta) synchronize to allow for information transfer from one brain region to another. In the Alzheimer’s mouse, however, gamma oscillations in the entorhinal cortex were impaired.

It was Igarashi’s postdoctoral advisors, the Mosers, who first identified cells in the entorhinal cortex that represent space using a grid pattern (dubbed grid cells). Disruption of the gamma rhythm in the same region could be a possible mechanism for spatial navigation deficits in Alzheimer’s patients. Next, he intends to stimulate the region to determine if the gamma rhythm can be restored. He hopes to accomplish these experiments in the coming months.

Just a synapse away from the entorhinal cortex is another region that is of particular interest to Igarashi. The piriform cortex, the olfactory center in the brain, has direct and privileged access to the entorhinal-hippocampal memory system. All other senses must funnel through the thalamus, traditionally thought to be a relay station (although admittedly it’s more complicated). Olfactory information, however, passes directly to the memory centers of the brain. Igarashi has his eye on this system as well, one that is known to be vulnerable in the early stages of Alzheimer’s disease. Using olfactory tasks with precisely timed odor delivery, he hopes to use a combination of electrophysiological recordings and optogenetics to better understand how this system operates and what features may be compromised in Alzheimer’s.

We walked across the hall to his lab where he took me on a quick tour. Immediately visible were two large computer monitors showing raw traces from the electrodes connected to his physiological recording equipment. Around the lab he had organized a surgical station, a T-shaped maze for behavioral tests in rodents, as well as an olfactory chamber. We then sat at his fabrication station, complete with tools and gadgets for building electrodes and machining electrical components.

“When you’re setting up a lab, no one gives you a shopping list,” he shrugged his shoulders. It was clear that he rose to the challenge quickly and set up his lab with state-of-the-art equipment. “And then of course, some things you have to make”, he demonstrated to me how to make a tetrode – four wires twisted around each other.

I marveled at the simplicity and asked “what does it do?” He laughed, “Everything!” He explained that this simple technology transformed the field by allowing investigators to identify individual cells firing by recording electrical activity in their vicinity. The tetrode was invented by another CNLM Fellow, distinguished professor Bruce McNaughton, one of the key reasons why Igarashi was motivated to come to Irvine. “It’s remarkable to be at the same institution with a pioneer like Bruce.”

As I watched him work the forceps deliberately and carefully under the microscope, I couldn’t help but notice the precision and fine motor skill needed for such work. I asked if this came naturally or took years of practice. “Both” he said, “but I played with Legos quite a bit as a kid.” I suspect it took a bit more than Legos to acquire these skills. Despite having students and postdoctoral fellows in the lab, Igarashi still spends considerable amounts of time in the lab himself, doing experiments, setting up rigs, building tetrodes, testing animals, and teaching his growing team how to use these techniques to address the scientific questions at hand.

Igarashi’s work on spatial processing in Alzheimer’s disease is clearly poised to transform the field and is gaining steady support. Most recently, he received a highly competitive seed grant to support his innovative work from the Brain Research Foundation, a nonprofit supporting neuroscience research. The first of many, he hopes. We hope so too.

Uncharted and unexplored as it may be, work by Igarashi and others stands to make the fundamental and translational neuroscience of space a little less of a mystery.

Click here to learn more about Dr. Igarashi’s research group.

BY: Manuella Yassa

CNLM Hosts the 30th Annual Conference on the Neurobiology of Learning and Memory

This month the Center for the Neurobiology of Learning and Memory hosted the 30th Annual Conference on the Neurobiology of Learning and Memory at the University of California, Irvine. The conference was attended by the Center’s Faculty Fellows, students, trainees and research scientists in addition to invited speakers from other institutions.

What makes some memories fleeting and others persistent? In 1890, William James suggested that memories, particularly emotional ones, can be so strong as to leave “a scar upon the cerebral tissues”. For centuries, the ability of salient experiences to leave behind persistent traces has captivated scientists and philosophers alike. While we now have a better understanding of the neural bases underlying the formation of many types of memory, the neural mechanisms of their persistence, and implications of this persistence for neuropsychiatric disorders have been subject to much debate. For example, it is not clear whether persistence and forgetting are active or passive processes at a physiological or biochemical level. Our understanding of how memory traces are transformed over time by repetition, rehearsal and reconsolidation (broadly defined) is also evolving and subject to conflicting views. The role of modulatory processes – including reward, stress, and fear – in making memories persistent is also a rapidly growing area of interest, with particularly important clinical implications. The 2017 Annual Meeting of the Center for the Neurobiology of Learning and Memory focused on this particular set of issues and facilitated a discussion of the state of the science, crucial unresolved questions, and experimental paths forward.

The conference featured three symposia that addressed this brand topic:
1. Persistence in rehearsal, retrieval and reconsolidation
2. Persistence of reward and addiction memories
3. Persistence of fear and stress memories

Day 1 of the conference began with a session titled “Persistence in rehearsal, retrieval and reconsolidation”, which included talks by Dr. Courtney Miller (Selective disruption of memories without retrieval), Dr. Gary Lynch (A new pathway-specific form of LTP related to episodic memory), and Dr. Michael Yassa (Repetition and semanticization of episodic memory). This session, moderated by Dr. James McGaugh, featured a debate among scholars regarding the very nature of lasting memories.

The second symposium of the day, titled “Persistence of reward and addiction memories” featured talks by Dr. Christie Fowler (Nicotine dependence and cholinergic signaling mechanisms: Implications for learning and memory), Dr. Steve Mahler (The Monkey sleeps lightly: pathological persistence of relapse risk in addiction), and Dr. Matt Lattal (Persistence extinction and the problem of relapse). The session, moderated by Dr. Marcelo Wood, grappled with the question “Is addiction a memory disorder?”

Day 2 began with a session moderated by Dr. Tallie Z. Baram titled “Persistence of fear and stress memories”. This session featured talks by Dr. Helen Scharfman (Estrogen and androgen induced persistent plasticity in hippocampal area CA3 and blockade by behavioral stress), Dr. Julie Lauterborn (Stress and synaptic actin signaling pathways involved in LTP), and Dr. Steve Maren (Neural circuits for fear relapse). The session focused on the impact of stress on memory and how sex differences modulate this relationship.

8 Faculty presented phenomenal Open Paper Talks (see below for titles)
Dr. Michel Baudry (A new link between calpain activation and tauopathy)
Dr. Jack Lin (Amygdala-hippocampal dynamics during salience processing)
Dr. Craig Stark (fMRS: Imaging memory-related neural activity in humans via dynamic measures of glutamate)
Dr. Marco Peters (PDE4d regulates spine plasticity and memory in the retrosplenial cortex)
Dr. Christine Smith (Conscious and unconscious memory as expressed in eye movements)
Dr. Kei Igarashi (Impaired in vivo gamma oscillations in the medial entorhinal cortex of knock-in Alzheimer model)
Dr. Christine Gall (Sexual dimorphism in synaptic mechanisms of encoding)
Dr. Xiangmin Xu (CA1-projecting subiculum neurons modulate spatial learning and memory)

16 Graduate Students and Postdoctoral Fellows presented Data Blitz’s
Terra White
, Guzowski Lab (Neuroimmune modulation of memory: From synapses to behavior)
Amy Frithsen, Stark Lab (Making memory decisions with highly superior autobiographical memory)
Yasaman Alaghband, Wood Lab  (The role of CREST in cocaine-associated memory formation)
Zachariah Reagh, Yassa Lab (The anterolateral entorhinal cortex and age-related memory decline)
Dane Clemenson, Stark Lab (Spatial exploration through Minecraft)
Thekla Hemstedt, Wood Lab (Importance of CREST for synaptic plasticity and memory formation)
Brittney Cox, Lynch Lab (Differential roles for the lateral and medial perforant pathways in a novel episodic memory task)
Rebecca Stevenson, Yassa Lab (Gamma and theta activity in the hippocampus and prefrontal cortex predict the precision of spatial memory retrieval)
Rianne Campbell, Wood Lab (Effects of chronic cocaine on Nr4a2 expression within the ventral tegmental area)
Megan Curran, Baram Lab (Mechanisms of memory problems after early-life seizures involve the neuronal repressor NRSF)
Geoffrey Diehl, J. Leutgeb Lab (Representation of space and features in the medial entorhinal cortex: Complementary coding by grid and nongrid cells)
Alberto Lopez, Wood Lab (The role of the medial habenula in regulating cocaine action)
Maria Montchal, Yassa Lab (Hippocampal correlations with sensory cortex as a function of memory precision)
Janine Kwapis, Wood Lab (Epigenetic regulation of the circadian gene Per1 underlies long-term memory formation)
Matthew Mahavongtrakul, Busciglio Lab (Genetic removal of synaptic zinc leads to cognitive impairment which can be prevented by Levetiracetam)
Dario Figueroa, Gandhi Lab (The reactivation of critical periods using interneuron transplantation)

Congratulations to the 2017 Data Blitz winners Janine Kwapis and Zachariah Reagh!

 

 The final discussion, “What makes some memories fleeting and others persistent” was co-moderated by Dr. Michael Yassa and Mr. Roger Bingham. A memorable moment was when James McGaugh asked “if memory is defined as an experience that changes memory, is a sunburn a memory?”

Next year’s CNLM annual meeting will be a larger, international conference and will be held at the Hilton Waterfront Resort in Huntington Beach April 18-22, 2018. Symposium submissions will open May 1, 2017.

More information can be found at www.learnmem2018.com

 

 

Colloquium Series

The CNLM Colloquium Series, supported by the Thomas Henry Curtis Fund, brings learning and memory scientists from around the world to UC Irvine. This lecture series is a great opportunity for faculty, students, trainees and research staff to learn about the latest in learning and memory research and gain feedback on their own work. Meeting with the speaker provides powerful network building opportunities for students and trainees and fosters future collaborations.

Location:
Dale Melbourne Herklotz Conference Center
Center for the Neurobiology of Learning and Memory)
(building 506 on the campus map)

Livestream:
Join the CNLM Seminars from anywhere in the world! Link to livestream will be available on the day of the colloquium. 

Upcoming Colloquia


Friday December 8, 2017 – 11AM 
(note alternate day/time)
Fabio Ferrarelli, M.D., Ph.D.
Assistant Professor
Psychiatry
University of Pittsburgh

Add to Calendar

Dr. Ferrarelli’s visit is jointly hosted by the UC Irvine School of Medicine’s Department of Psychiatry and Human Behavior and the Center for the Neurobiology of Learning and Memory

Sleep spindle deficits in schizophrenia: when do they start?
Sleep spindles are waxing and waning, 12-16 Hz oscillations, occurring during NREM sleep. Spindles are generated by the interplay of the Thalamic Reticular Nucleus (TRN) with the dorsal thalamus, and are then relayed to, and amplified within the cortex. While their functional role has yet to be fully elucidate, recent evidence indicates that spindles are associated with cognitive ability, schizotypal traits, and social functioning in healthy controls (HC), including adolescents and young adults. In previous work, by employing high density (hd)-EEG we established deficits in spindle amplitude, density, duration, and Integrated Spindle Activity (ISA) in centro-parietal and prefrontal regions of chronic patients with schizophrenia (SCZ) compared to both HC and non-schizophrenia psychiatric patients. A reduction in spindle amplitude and density was also recently reported in first episode SCZ, with EEG recordings performed on two central channels (C3, C4). Although promising, these findings leave a number of unanswered questions, including: 1) What is the spatial distribution of spindle deficits at illness onset? 2) Which are the most defective spindle parameters at that stage? 3) When do spindle deficits begin in relation to the development of SCZ and related disorders? Here, after reviewing previous findings on sleep spindle deficits in SCZ, I will present novel results of an ongoing study in first-break psychosis patients, as well as discuss a recently NIMH funded project investigating spindle activity in individuals at high risk for SCZ and other psychotic disorders, which should begin to answer some of these queries.

 

Monday January 8, 2018 – 4PM (note alternate day/time)
Loren Frank, Ph.D.

Professor
Howard Hughes Medical Institute
Kavli Institute for Fundamental Neuroscience
University of California, San Francisco
Dr. Frank’s visit is co-hosted by the Medical Science Training Program, Department of Anatomy and Neurobiology and the Center for the Neurobiology of Learning and Memory

Neural substrates of memories and decisions

Tuesday January 30, 2018 – 11AM
Majid Mohajerani, Ph.D.

Assistant Professor
Canadian Center for Behavioral Neuroscience
University of Lethbridge
More info coming soon!

 

Tuesday February 13, 2018 – 11AM
Mara Mather, Ph.D.
Professor of Gerontology and Psychology
Leonard Davis School of Gerontology
University of Southern California
More info coming soon!

 

Tuesday February 20, 2018 – 11AM
Betsy Murray, Ph.D.
Chief
Section on Neurobiology of Learning and Memory
Laboratory of Neuropsychology
National Institute of Mental Health
More info coming soon!

 

Tuesday May 1, 2018 – 11AM
Linda Levine, Ph.D.
Professor
Psychology and Social Behavior
University of California, Irvine

More info coming soon!

 

 


Past Colloquia

CNLM Colloquium Series 2017-2018

Wednesday November 1, 2017 – 10AM (note alternate day/time)
Mark Gluck, Ph.D.

Co-Director, African American Brain Health Initiative
Professor of Neuroscience
Center for Molecular & Behavioral Neuroscience
Rutgers University


Fitness and lifestyle affect neural and cognitive risk factors for Alzheimer’s Disease in older African Americans
In cross-sectional, longitudinal  and interventional studies, we are examining how fitness and lifestyle affect neural and cognitive risk factors for Alzheimer’s Disease. Over the past 12 years, the African American Brain Health Initiative: A University-Community Partnership at Rutgers University-Newark  has worked with local churches, senior centers, and low-income housing, along side city, county, and state agencies for aging and health, to promote improved brain health and reduce risk for Alzheimer’s Disease among older African Americans in Greater Newark, New Jersey. Our cross-sectional and longitudinal studies (funded by NIH/NIA) seek to understand how physical fitness affects both cognitive and neural markers for Alzheimer’s risk. Our interventional research (funded by the NJ Dept. of Health) examines how these markers change following five months of twice-weekly dance-based exercise. The cognitive assessments and brain imaging studies build on Gluck and colleagues prior animal, human, and neurocomputational studies of the role of the hippocampus and related medial temporal lobe structures in mediating stimulus representation and generalization in cognitive skill learning.

Tuesday October 24, 2017 – 11AM
Elly Nedivi, Ph.D.

Professor of Brain & Cognitive Sciences and Biology
The Picower Institute for Learning and Memory
Massachusetts Institute of Technology



Visualizing Synapse Structural Dynamics in vivo
The introduction of two-photon microscopy for in vivo imaging has opened the door to chronic monitoring of individual neurons in the adult brain and the study of structural plasticity mechanisms at a very fine scale. Perhaps the biggest contribution of this modern anatomical method has been the discovery that even across the stable excitatory dendritic scaffold there is significant capacity for synaptic remodeling, and that synaptic structural rearrangements are a key mechanism mediating neural circuit adaptation and behavioral plasticity in the adult. To monitor the extent and nature of excitatory and inhibitory synapse dynamics on individual L2/3 pyramidal neurons in mouse visual cortex in vivo, we labeled these neurons with a fluorescent cell fill as well as the fluorescently tagged synaptic scaffolding molecules, Teal-Gephyrin to label inhibitory synapses, and mCherry-PSD-95 to label excitatory synapses. We simultaneously tracked the daily dynamics of both synapse types using spectrally resolved two-photon microscopy. We found that aside from the lower magnitude of excitatory synaptic changes in the adult, as compared to inhibitory ones, excitatory synapse dynamics appear to follow a different logic than inhibitory dynamics. While excitatory dynamics seem to follow a sampling strategy to search for and create connections with new presynaptic partners, inhibitory synapse dynamics likely serve to locally modulate gain at specific cellular locales.

Tuesday October 17, 2017 – 11AM
David Reinkensmeyer Ph.D.

Professor
Mechanical and Aerospace Engineering
Biomedical Engineering
University of California, Irvine

Robotic assistance during movement training after stroke: A Hebbian Model?
In this talk I will first provide a brief overview of the evolution o the technology and science of robotic-assisted rehabilitation after stroke over the past twenty years.  Then I will discuss a recent study in which we compared the therapeutic effects of high and low levels of robotic assistance during finger training. Participants (n = 30) with a chronic stroke and moderate hemiparesis actively moved their index and middle fingers to targets to play a musical game similar to GuitarHero three hours/week for three weeks. The FINGER exoskeleton robot provided assistance synchronized to the music; half of the participants were randomized to receive high assistance (causing 82% success at hitting targets), while the other half received low assistance (55% success). High levels of synchronized assistance boosted motivation, as well as secondary motor outcomes (Fugl-Meyer and Lateral Pinch Strength) – particularly for individuals with more severe finger motor deficits. Importantly, individuals with impaired finger proprioception at baseline benefited substantially less from the training. These results show that synchronized robotic assistance can promote psychological outcomes known to modulate motor learning and retention. Further, the therapeutic effectiveness of synchronized robotic assistance may derive at least in part from proprioceptive stimulation, consistent with a Hebbian plasticity model.  I will conclude by presenting data showing extreme motor learning by people with very severe arm impairment after stroke, using a novel bimanual lever drive wheelchair.

 

CNLM Colloquium Series 2016-2017

buffaloTuesday May 2, 2017 – 11AM
Elizabeth Buffalo, Ph.D.
Associate Professor, Department of Physiology and Biophysics
University of Washington School of Medicine

 

Bridging the gap between the spatial and mnemonic views of the hippocampus​.

While it has long been recognized that medial temporal lobe structures are important for memory formation, studies in rodents have also identified exquisite spatial representations in these regions in the form of place cells in the hippocampus and grid cells in the entorhinal cortex. Spatial representations entail neural activity that is observed when the rat is in a given physical location, and these representations are thought to form the basis of navigation via path integration. One striking difference between rodents and primates is the way in which information about the external world is gathered.  Rodents typically gather information by moving to visit different locations in the environment, sniffing and whisking.  By contrast, primates chiefly use eye movements to visually explore an environme
nt, and our visual system allows for inspection of the environment at a distance. In this seminar, I will discuss recent work from my laboratory that has examined neural activity in the hippocampus and adjacent entorhinal cortex in monkeys performing behavioral tasks including free-viewing of complex natural scenes and navigation in a virtual environment. These data have suggested that spatial representations including place cells, grid cells, border cells, and direction-selective cells can be identified in the primate hippocampal formation even in the absence of physical movement through an environment. I will also discuss new research involving chronic, large-scale recordings throughout the primate brain and other areas of opportunity for future research to further our understanding of the function of the hippocampal formation and the nature of the cognitive map.

eichenbaum

Tuesday April 25, 2017 – 11AM
Howard Eichenbaum, Ph.D.
Professor of Psychological and Brain Sciences
Director, Center for Memory and Brain
Director, Cognitive Neurobiology Laboratory
Boston University

The hippocampus: Mapping memories in space and time
Many studies have identified neurons in the hippocampus and associated cortical areas as coding for locations in space (i.e., place cells and grid cells), leading some to view the hippocampus as dedicated to mapping space and supporting spatial navigation. Here I will argue an alternative view that populations of hippocampal neurons create a highly organized mapping of important events in the places and meaningful contexts in which they occur. Furthermore, I will describe recent evidence that hippocampal “time cells” in both the hippocampus and associated cortical areas encode specific moments in a temporally structured experience, much as place and grid cells encode locations in spatially structured environment. And I will describe how time cell ensembles encode the temporal organi
zation of specific memories and predict memory success. These findings support of an emerging view that the hippocampus serves memory (and navigation) by mapping the organization of events within their spatial and temporal context.

SpitaleTuesday February 21, 2017 – 11AM
Robert Spitale, Ph.D.
Assistant Professor of Pharmaceutical Sciences and Chemistry
University of California, Irvine

 

Emerging Chemical Tools for Studying RNA: Applications to Neuroscience?
Synopsis: RNA molecules play critical roles in nearly every cellular pathway. They have been demonstrated to be critical to the onset of many neurological disorders and diseases. Despite their importance there is a real lack of tools to study their biology at high precision. Within this presentation I will detail some of our labs ongoing work, and what we hope to achieve in the near future. I will also outline how what we are developing can be applied to some of the longest standing questions in nueroscience, on the molecular scale.


Jason_Shepherd

Tuesday, November 1, 2016 – 11AM
Jason Shepherd, Ph.D.
Assistant Professor of Neurobiology and Anatomy
Adjunct Professor of Ophthalmology and Visual Sciences
University of Utah, School of Medicine

 

Retroviral Origins of Synaptic Plasticity
Memories are stored in specific patterns of synaptic connections that occur through changes in synaptic strength, which rely on the addition or removal of AMPA-type glutamate receptors (AMPARs) from postsynaptic membranes. The immediate early gene Arc plays a critical role in multiple forms of synaptic plasticity, but the underlying molecular mechanisms remain unclear. Here we describe novel findings that Arc protein acts like the GAG retrovirus poly-peptide to control synaptic plasticity. Using cryo-electron microscopy we show that Arc forms viral capsid-like oligomers, which bind lipid membranes and RNA. Our studies elucidate the processes that underlie protein-synthesis dependent synaptic plasticity and may have uncovered a specialized neuronal trafficking pathway that has unique biochemistry similar to viral infection and replication.


manderSpecial Colloquium co-hosted by the CNLM and the Department of Psychiatry and Human Behavior
Tuesday, October 11, 2016 – 11AM

Bryce Mander, Ph.D.
University of California, Berkeley

 

Neural correlates of age-related disruption of sleep oscillation expression and sleep-dependent memory
Sleep changes with age, becoming more fragmented, less organised, shorter in duration, and less densely-packed with the signature sleep oscillations, sleep spindles and slow waves, which causally promote memory consolidation. Despite the established role of sleep, and in particular slow waves and sleep spindles, in memory processing across the lifespan, how age-related changes in the brain ultimately impact slow wave and sleep spindle expression remains unclear. In this lecture, I will review our recent work examining how age-related changes in brain structure and neuropathology impacts slow wave and sleep spindle expression, ultimately impacting memory-related activation within the hippocampus. Embedded in a larger literature, these findings help to clarify how sleep changes with age may contribute to age-related memory decline, and offer novel treatment targets to preserve memory in later life.


 

CNLM Colloquium Series 2015-2016

 igarashiWednesday, April 20, 2016, 4 p.m.
Kei Igarashi, Ph.D.
Department of Anatomy and Neurobiology, University of California, Irvine

Dissecting sensory-hippocampal circuit interactions during associative learning
Declarative memory is enabled by circuits in the entorhinal cortex (EC) that interface the hippocampus with the neocortex. During encoding and retrieval of declarative memories, entorhinal and hippocampal circuits are thought to interact via theta and gamma oscillations, which in awake rodents predominate frequency spectra in both regions. Using multisite recording at successive stages of associative learning, we found that the coherence of beta/gamma oscillations in directly-connected entorhinal-hippocampus circuits evolves as rats learn to use an odor cue to guide navigational behavior, and that such coherence is linked to the development of ensemble representations for unique trial outcomes in each area. These results point to 20-40 Hz oscillations as a mechanism for synchronizing evolving representations in dispersed neural circuits during encoding and retrieval of olfactory-spatial associative memory. Potential roles of 20-40 Hz oscillations for circuit plasticity, as well as future perspective on olfactory-hippocampal circuit analyses will be discussed.


ParviziMonday, March 28, 2016, 4 p.m.
Josef Parvizi, M.D., Ph.D.
Department of Neurology and Neurological Sciences, Stanford University

Numbers in the human brain: Eavesdropping on the activity of discrete populations of neurons in the human brain during arithmetic processing
I will present a historical overview of localization of functions in the brain and review some of our most recent studies with intracranial electrocorticography (ECoG) and electrical brain stimulation (EBS) in patients implanted with intracranial electrodes to shed new light on some of the open questions in the field of cognitive neuroscience, especially when it comes to mathematical processing. For instance, which regions are at play when we put 2 and 2 together and how are they working together. I will present some of our most recent data from experimental as well as naturalistic conditions and will present videos of patients during ECoG and EBS procedures.

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Tuesday, February 9, 2016, 4 p.m.
Jay McClelland, Ph.D.
Department of Psychology and Center for Mind, Brain, and Computation, Stanford University

Integrating Rapid Neocortical Consolidation into Complimentary Learning Systems Theory
Since the 1950’s, it has been known that the medial temporal lobes in the brain play a special role in learning and memory. These findings have led, through the work and thinking of David Marr and many others, to a theory of the roles of hippocampus and neocortex in memory called the complementary learning systems theory (McClelland, McNaughton, & O’Reilly, 1995). Our theory postulated two distinct learning systems, one in the medial temporal lobes that supports the rapid learning of arbitrary new information, and one in the neocortex and other structures that supports the gradual discovery of structured representations that encode knowledge of the natural and man-made world, as well as the knowledge underlying cognitive skills and the knowledge underlying language and communication. In this talk, I examine evidence from recent studies showing that new information can sometimes be integrated rapidly into the neocortex, challenging our theory as previously presented. I present new simulations based on our theory, showing that new information that is consistent with knowledge previously acquired by a cortex-like artificial neural network can be learned rapidly without interfering with existing knowledge. These results match the pattern observed in the recent studies, and provide a mechanism for understanding when and how rapid integration of new information can occur.

Knight

Thursday, December 10, 1 p.m.
Robert T. Knight, M.D.
University of California, Berkeley

Frontal Cortex Physiology and Human Behavior

 

 

 

 

large_Sheri

Thursday, November 19, 4p.m.

Sheri J.Y. Mizumori, Ph.D.
University of Washington

Hippocampal neural activity reflects the economy of choices
Hippocampal neural activity patterns are context-dependent, and this may aid in the formation of episodic memories. Distinguishing contexts requires an ability to recall features of a learned context, then compare the predicted features to those actually experienced. We studied how hippocampus represents predicted context information. Hippocampal place cells and theta activity were recorded during the performance of a maze-based probability discounting task in which predictive information about the probability of reward was systematically varied. Place fields redistributed (or remapped) around the goal location, but only during low probability trials that ended with reward delivery. Also around the goal location, theta power increased in proportion to the expected probability of reward, and not sensory or behavioral modulation. Theta power further dynamically varied as specific econometric information was obtained ‘on the fly’ during task performance. Behavioral economic information may define a ‘decision context’ that guides hippocampal context-dependent representations and learning during navigation.

medium_MeckThursday, May 14, 4 p.m.
Warren H. Meck, Ph.D.
Duke University
Functional and Neural Mechanisms of Interval Timing
The ability of the brain to process time in the seconds-to-minutes range is a fascinating problem given that the basic electrophysiological properties of neurons operate on a millisecond time scale. Neuropsychological studies of humans and other animals with damage to the basal ganglia have indicated that these structures play an important role in timing and time perception. Parkinson’s disease patients, for example, show evidence of a slowed internal clock and the “coupling” of durations stored in temporal memory when tested off of their dopaminergic medication. These studies have shown that the normal cognitive functions of the basal ganglia are heavily dependent upon dopamine-regulated neuronal firing in the cortex and striatum. Moreover, the electrophysiological properties of striatal medium spiny neurons within the basal ganglia suggest that these neurons may serve as a coincidence detectors of cortical and thalamic oscillatory input in order to provide the basis for duration discrimination in the seconds-to- minutes range. Recent findings obtained from ensemble recording in the prefrontal/cingulate cortex and the anterior dorsal striatum of rats performing in peak-interval timing procedures indicate that striatal neurons are able to encode specific durations in their firing rate in a “perceptron-like” manner. These findings correspond well with fMRI data obtained from human participants performing similar timing tasks and lend support to the striatal beat-frequency model of interval timing.

CNLM Colloquium Series 2014

charleslimoli

Thursday, January 16, 11am
Charles Limoli, Ph.D.
University of California, Irvine
Radiation- and chemotherapy-induced cognitive dysfunction: Causes, consequences and treatments
Exposure of the CNS to treatments used to control the advance of cancer has been known to compromise cognitive function. Depending on disease state, treatments specifics and socioeconomic factors, cognitive outcomes vary in onset and severity. With increasing numbers of cancer patients surviving long-term, cognitive health is becoming an increasing concern, and to date, no satisfactory treatments exist for ameliorating the progressive and often debilitating cognitive side effects caused by radiotherapy and chemotherapy. This talk will cover the various mechanisms underlying treatment associated cognitive dysfunction and discuss the potential of using stem cell based strategies for the long-term treatment of this serious unmet medical need.

routtenbergThursday, March 13, 11am
Aryeh Routtenberg, Ph.D.
Northwestern University
Is mamallian NMDA-dependent long-lasting memory conserved in C. elegans?
The N-methyl-D-aspartate receptor (NMDA-R) is associated with memory formation in both vertebrate and invertebrate nervous systems suggesting evolutionary conservation of this receptor mechanism. While considerable information exists concerning vertebrate NMDA-R and memory, evidence for its role in invertebrates is sparse; hence its linkage to mammalian mechanisms remains poorly understood.  To begin to address this issue, we studied the formation of long-term associative memory as regulated by NMDAR and its subunit NMR-1 in the nematode, Caenorhabditis elegans (C. elegans).

frankThursday, March 20, 11am
Loren Frank, Ph.D.
University of California, San Francisco
Neural substrates of memory retrieval and decision-making
The hippocampus is a brain structure known to be critical for forming and retrieving memories for the experiences of daily life, but the specific patterns of neural activity that support memory formation and retrieval remain unclear.  In this talk I will discuss work from my laboratory that links a specific pattern of hippocampal place cell activity to the ability to use past experience to guide behavior.  We have shown that hippocampal replay events can reactivate patterns of brain activity from a previous experience in awake animals and that disrupting these events interferes with learning and memory-guided decision-making.  Further, we have found that the intensity of replay activity is predictive of whether an upcoming choice will be correct or incorrect. Our results suggest that the awake replay of place cell sequences plays a role in deliberative proceeses that are important for memory-guided decision making.

Faculty Fellows

Who are our Faculty Fellows?

Our Resident Fellows are faculty at the University of California, Irvine (UCI) in the departments of Neurobiology and Behavior, Neurology, Cognitive Sciences, Pharmacology, Psychiatry and Human Behavior, Psychology and Social Behavior and Anatomy and Neurobiology.

Our External Fellows are faculty at various institutions around the world. 

Newly Inducted Fellows

The CNLM is delighted to welcome our newest Fellows! You will be hearing more about their work in our upcoming newsletter! Nomination and subsequent election to the CNLM Fellowship is a distinguished honor based on majority voting by the current Fellows. All active Fellows contribute to the scientific excellence of the Center.

Ted Abel

Timothy Allen Ruth Benca Federico Bermudez-Rattoni

Kasia Bieszczad

Jennifer Bizon

Sara Burke Laura Colgin Paul Gold

Ivan Izquierdo

Jack Lin

Aaron Mattfeld Andrew Maurer Richard Morris

David Reinkensmyer

Barry Setlow Wendy Suzuki

 

CNLM Fellows

AdolphsRalph ANAGNOSTARAS alkire baram mbaudry
Ralph Adolphs Stephan Anagnostaras Michael Alkire Tallie Z. Baram Michel Baudry
bredy busciglio cahill ProfClark-1 cohen-cory
 Timothy Bredy Jorge Busciglio Lawrence Cahill Robert Clark Susana Cohen-Corey
cramerk Dr. Steven Cramerphoto by Steve Zylius/UCI communications dosher Michael-Fanselow-400x400_0 fortin
Karina Cramer Steven Cramer Barbara Dosher Michael Fanselow Norbert Fortin
Fowler_Headshot2015 76841_cover2 259_Fuster_Photo_2 Christine_Gall gandhi
 Christie Fowler Ron Frostig Joaquin Fuster Christine Gall Sunil Gandhi
JohnGuzowski_web Hickok igarashi jaeggi-susanne2014_small kawas
John Guzowski  Gregory Hickok Kei Igarashi Susanne Jaeggi Claudia Kawas
s200_barbara-knowlton LaFerla_crop leon jleutgeb sleutgeb
Barbara Knowlton Frank LaFerla Michael Leon Jill Leutgeb Stephan Leutgeb
loftus-1 garylynch mahler martin_10_18
Charles Limoli Elizabeth Loftus Gary Lynch Steve Mahler Kelsey Martin
mayford mcgaugh_head bruce_mcnaughton metherate john
Mark Mayford James McGaugh Bruce McNaughton Raju Metherate John O’Doherty
Daniele Piomelli in his lab in Italy. silva2 squire Steve-Small Soltesz
Daniele Piomelli Alcino Silva Larry Squire Steve Small Ivan Soltesz
stark steward Georg thompson dickthompson
Craig Stark Oswald Steward Georg Striedter Leslie Thompson Richard Thompson
wiltgen Norman_Weinberger Dr.-Wood-04-11-14 XiangminXu0508B mike_director-e1472702114183-300x245
Brian Wiltgen Norman Weinberger Marcelo Wood Xiangmin Xu  Michael Yassa