# Dorsoventral functional divergence of the hippocampal CA3 circuit

> **NIH NIH K01** · CASE WESTERN RESERVE UNIVERSITY · 2021 · $44,888

## 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:** 10406500
- **Project number:** 3K01MH117444-03S1
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Qian Sun
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $44,888
- **Award type:** 3
- **Project period:** 2021-08-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10406500

## Citation

> US National Institutes of Health, RePORTER application 10406500, Dorsoventral functional divergence of the hippocampal CA3 circuit (3K01MH117444-03S1). Retrieved via AI Analytics 2026-06-23 from https://api.ai-analytics.org/grant/nih/10406500. Licensed CC0.

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