Park City Winter Conference

2024 Conference Program

Thursday, January 4, 2024

Session 1 (4-6 PM): Dave Olton Data Blitz
Prospector 2 & 3

Session 2 (8-10 PM): New insights into in vivo functions of adult hippocampal neurogenesis.
Co-chairs: Sebnem Tuncdemir & Tiago Goncalves

Kimberly M. Christian – University of Pennsylvania
Sebnem N. Tuncdemir – University of Connecticut School of Medicine
Paul Frankland – University of Toronto
Juan Song – University of North Carolina

The hippocampal dentate gyrus exhibits a unique form of neural plasticity that results from the continuous integration of adult born granule cells (abGCs), termed adult neurogenesis. Although it is now clear that the highly excitable and plastic adult born neurons are critical for hippocampus-mediated learning and memory guided behaviors, exactly how they influence hippocampal representations is poorly understood. Speakers in this session will present recent work using novel in vivo approaches to monitor and manipulate abGCs, demonstrating complementary facets of their functional integration into
adult hippocampal circuits. These studies will be presented by a mix of early-and mid-career faculty, as well as established investigators who are leaders in the field from diverse backgrounds. The discussion will highlight shared findings across these varied approaches, building toward a unified perspective
on how abGCs function and develop in vivo, and whether they encode information differently from mature granule cells. We will also emphasize key points of disagreement and discuss experimental and analysis strategies that can reconcile the different findings in this field.

Friday, January 5, 2024

Session 3 (8-10am): The cellular and molecular mechanisms that determine accurate memory retrieval
Chair: Seetha Krishnan

Seetha Krishnan – University of Chicago
Can Dong – Stanford University
Edward Nieh – University of Virginia
Prerana Shrestha – Stony Brook University

A memory trace triggers molecular, cellular and circuit level changes in widespread networks of neurons throughout the brain. A key challenge in memory research over the years has been to understand how these different processes contribute to the formation and consolidation and thereby the accurate retrieval of a memory. Novel techniques, specifically optical and genetic tools have allowed us to update our models on how memories persist at the neural circuit level and offered new insights into the dynamic nature of memory. Here, we present our work, using these new techniques on how a particularly strong
fear memory drives changes in the brain and highlight some of the specific processes that determine how well this strong memory will be stored and retrieved. The first two talks will focus on cellular and systems level processes in the brain that occur during memory formation that are important for retrieval. Dr. Krishnan and Dr. Dong’s work utilizes two-photon imaging at single cell resolution and a novel behavior paradigm to study fear conditioning. They will show that during fear memory formation synchronized activity increases between single neurons in the CA1 and CA3 subregion of the hippocampus. The frequency of these synchronizations predicts how well the memory is retrieved by the
animal the following day. Dr. Nieh’s work employs computational tools and non-linear dimensionality reduction techniques on large neuronal ensembles. He will show that the activity across populations of neurons in both the hippocampus and the Nucleus Accumbens are constrained to lowdimensional manifolds during fear conditioning. Furthermore, he will show that critical for the learning of this task is a change in the dimensionality. The final two talks will focus on the molecular and synaptic changes that occur during memory consolidation that determine memory retrieval. Dr. Shrestha’s talk will feature novel chemogenetic tools that block cell-type specific protein synthesis in behaviorally relevant epochs. Using these tools, her findings reveal that disrupting nascent protein synthesis during memory consolidation specifically in excitatory neurons in the prelimbic cortex attenuates long-term memory retrieval. Finally, Dr. Frick will show that estrogen plays a critical role in modulating the molecular processes in the hippocampus that lead to memory consolidation. Her work reveals how aging related loss of estrogen in females can result in dysfunctions in memory retrieval. With this panel, we aim to bring forth multi modal discoveries on how a memory trace gets incorporated into the brain and present a small snapshot of the many factors that determine whether it will be accurately retrieved later. Our inter-disciplinary panel will garner the interest of many in the audience and we hope to generate discussion on a variety of topics including what exactly is a memory trace in the brain, why is it so labile, what factors determine whether a strong memory will be retrieved in the future, how do these factors change with the aging brain, what are the changes to the molecular machinery within the cell in response to a strong memory, how can we
translate these findings to improve memory retrieval, etc.

Session 4 (4-6pm): Memory Storage: Dynamic Ensembles or Static Synapses? Part 1: Dynamic ensembles
Chair: Denise Cai

Evan Schaffer – Mt Sinai
Kari Hoffman – Vanderbilt University
Priya Rajasethupathy – Rockefeller University
Mazen Kheirbek – University of California, San Francisco

How are memories stored in the brain? This has been a major debate for centuries. The memory “engram” model asserts that synaptic plasticity rewires groups of neurons to form a specific circuit or ensemble that remains stable for up to a lifetime. However, in vivo evidence for stable synapses has been lacking. Does a memory storage mechanism require molecular and structural changes that endure, and if so, where? Recent evidence suggests that memory ensembles in the brain “drift”, despite the behavioral expression of the memory being stable. This suggests that the memory circuit is dynamic and not fixed. The goals of these sessions are to explore how memories are stably stored while neural ensembles are dynamically drifting.

Session 5: (8-10pm) Memory Storage: Dynamic Ensembles or Static Synapses? Part 2: Static Synapses
Chair: Jason Shepherd

Tomas Ryan – Trinity College Dublin
Rick Huganir – Johns Hopkins University
Ulli Bayer – University of Colorado
Megha Sehgal – UCLA

Saturday, January 6, 2024

1:00pm NEW: Professional Development Lunch
Panel: Sheri Mizumori, Moriel Zelikowsky, Aqilah McCane, Denise Cai

The 2024 meeting will feature our inaugural professional development event for graduate student and postdoctoral trainees! A Career Panel will include Aqilah McCane (OHSU), Moriel Zelikowsky (UUtah), Denise Cai (Mt. Sinai), and Sheri Mizumori (UWash).  It will be held Saturday January 6th, 1:00pm at the Park City Sheraton. Lunch will be provided. After you register for the conference, please use this link to register for the Career Panel: https://docs.google.com/forms/d/e/1FAIpQLScC2vzDh-GNYFapSvN6yJwAz0n2MmPqDQeTg6YViSV6fesQtg/viewform?usp=sf_link

Session 6 (4-6pm): Understanding how memories are modified across the lifespan
Chair: Janine Kwapis

Janine Kwapis – Pennsylvania State University
Sydney Trask – Purdue University
Boyer Winters – University of Guelph
Autumn Ivy –  University of California, Irvine

Memories are not stored as fixed records of experience, but are dynamically modified to incorporate new, relevant information. While the mechanisms that support de novo memory formation are well-characterized, much less is known about how existing memories are updated with new information. This session will focus on mechanisms that enable memory modification across levels of analysis, from behavioral models to neuronal ensemble dynamics to changes in gene and protein expression. We will also consider how this process changes across the lifespan, from development through adulthood and impairments in memory updating that occur in old age. Discussion will seek to identify the difference between memory formation and memory updating, compare and contrast mechanisms important for updating from those needed for initial memory formation, describe how these mechanisms change with age, and identify commonalities in memory updating across different tasks and levels of analysis.

Banquet, 7:30pm

Sunday, January 7, 2024

Session 7 (4-6pm): Memory circuits and their role in neurological disorders
Co-chairs: Tristan Shuman & Steve Ramirez

Tristan Shuman – Icahn School of Medicine at Mount Sinai
Steve Ramirez – Boston University
Holly Hunsberger – Rosalind Franklin University
Annabelle Singer – Emory University

The goal of our session is to explore basic circuit mechanisms that lead to successful memory encoding, maintenance, and retrieval, and how these processes break down across neurological disorders. Memory deficits are a hallmark of several neurological disorders including Alzheimer’s disease and epilepsy and understanding the specific mechanisms that contribute to cognitive deficits can provide new insight into basic memory processes and also lead to new circuit therapeutics. Our session will focus primarily on rodent models of memory and neurological disorders and will span many levels of investigation including behavioral, cellular, and molecular approaches. Together, our speakers have expertise in imaging, electrophysiology, transcription profiling, and have recent work focusing on how memory mechanisms break down in Alzheimer’s disease and/or epilepsy.

Session 8 (8-10pm): Trauma Altered Neurobiology: A detailed perspective on how trauma alters the brain
Chair: Kevin Sattler

Kevin Sattler – University of Utah
Kerry Ressler – McLean Hospital; Harvard Medical School
Beka Stecky – Columbia University
Rebekah Rashford – Princeton University

While Posttraumatic Stress Disorder (PTSD) was not added to the Diagnostic and Statistical Manual of Mental Disorders until 1980, trauma related disorders have been discussed in literature since the Epic of Gilgamesh. Although trauma-related symptoms have existed as long as humanity, we still have a relatively poor understanding of how a traumatic experience can lead to a diverse set of negative behavioral phenotypes. Some of the most common symptoms of trauma-related disorders include inappropriately enhanced fear responses, avoidance behaviors, altered memory, changes in social behavior, and unwarranted increases in aggression, however the neuronal circuitry underlying these diverse changes in behavior have not yet been elucidated. Here, we aim to discuss the processes by which the brain responds to extreme stress, including early life stress and epigenetic inheritance (Dr. Mansuy), increased vulnerability to develop trauma-related disorders (Dr. Rajbhandari), specific neural circuits underlying individual trauma-altered behaviors (Kevin Sattler), and the transection between animal model research and translational research leading to improved healthcare outcomes (Dr. Ressler). We would like to use this session to lead a dialogue about what we do understand about trauma processing and what we can do as scientists to lead to real change regarding the perception of trauma related health disorders.