# Dorsoventral functional divergence of the hippocampal CA3 circuit

> **NIH NIH K01** · CASE WESTERN RESERVE UNIVERSITY · 2020 · $148,989

## Abstract

PROJECT SUMMARY/ABSTRACT
My career goal is to lead an independent research group to investigate the cellular and circuit
mechanisms underlying normal operation of the hippocampal CA3 circuit and the role of CA3 in
neuropsychiatric disorders, such as depression and schizophrenia. To achieve this goal, I propose a
project that will provide me with significant training by investigating the dorsoventral divergence of
hippocampal CA3 function. The CA3 area of the hippocampus is traditionally viewed as a
homogeneous autoassociative network crucial for rapid associative learning and memory. However,
my recent work and others have demonstrated a remarkable transverse heterogeneity in intrinsic
excitability, synaptic connectivity, and behavior in dorsal CA3. This proposal follows up and expands
on these previous studies to test a central hypothesis that the dorsal and ventral CA3 are differentially
involved in contextual learning and anxiety-related behavior. Specifically, I propose to differentiate the
behavioral role of dorsal versus ventral CA3 using channelrhodopsin2 (ChR2)-based optogenetic and
Designer Receptors Exclusively Activated by Designer Drugs (DREADDs)-based chemogenetic
approaches to bidirectionally manipulate dorsal versus ventral CA3 activity. Next, I will employ an
immediate early gene Arc-based memory tagging strategy to test whether activation of memory
engram cells in dorsal or ventral CA3 is sufficient to recall a fear memory. Finally, I will utilize in vivo
miniature microscope imaging technology to examine whether the dorsal and ventral CA3 display
distinctive network dynamics that underlie their specific behavioral function. Taken together, the
proposed experiments will provide new insight into the diversity of in vivo operation and behavioral
function of CA3 circuit. Moreover, as certain neuropathological conditions, such as chronic stress,
depression, and schizophrenia, preferentially impair dorsal or ventral hippocampus, this proposal is
highly relevant to clinical research. As my primary expertise has been in neurophysiology, the
proposed studies represent a significant change of my research and will enable me to acquire
essential new training in mouse behavior, in vivo imaging, and large-scale data analysis. My career
goal is to combine these technique and scientific insights gained through this K01 to provide a better
understanding of how CA3 circuit operates under physiological condition and how a dysfunctional
CA3 circuit leads to behavioral deficits in CA3-related neuropsychiatric disorders, such as depression
and schizophrenia.

## Key facts

- **NIH application ID:** 9760000
- **Project number:** 5K01MH117444-03
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Qian Sun
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $148,989
- **Award type:** 5
- **Project period:** 2019-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9760000

## Citation

> US National Institutes of Health, RePORTER application 9760000, Dorsoventral functional divergence of the hippocampal CA3 circuit (5K01MH117444-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9760000. Licensed CC0.

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