# Inhibitory regulation of hippocampal CA3 neuron activity, learning, and memory

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2024 · $573,612

## Abstract

PROJECT SUMMARY/ABSTRACT
Inhibitory GABAergic neurons comprise only about 15% of all neurons in the brain yet their activity
is critical for all aspects of brain function and GABA neuron dysfunction is implicated in many
neurological disorders and mental illnesses. In particular, inhibition likely plays a unique and
important role in hippocampal area CA3. In the CA3 region, DG neurons synapse onto CA3
pyramidal neurons via giant excitatory mossy fiber terminals and CA3 neurons make many
recurrent connections. Thus, the potential for runaway excitation in CA3 is high. Feed-forward
inhibition from DG to CA3 is thought to be critical allow specific excitatory inputs to generate
meaningful activity patterns. Despite the likely importance of inhibition in hippocampal area CA3,
few studies have directly examined how GABA neuron activity controls CA3 pyramidal neuron
activity. We identified a group of dendrite-targeting GABA neurons that commonly express the
synaptogenic protein Kirrel3. Kirrel3 protein is necessary to form MF filopodia synapses, a special
type of excitatory synapse that connects DG neurons to GABA neurons and mediates feed-
forward inhibition to CA3. Because Kirrel3 must be expressed in both the pre- and post-synaptic
neuron to make a synapse, it strongly suggests Kirrel3-expressingn GABA neurons are direct
targets of MF filopodia and the study of K3-GABA neurons will shed light on the precise function
of MF filopodia-mediated inhibition in CA3. We will test this in three aims spanning ultrastructural
analysis to large-scale functional cell imaging to behavior. Throughout, we will examine the
selectivity of this group of dendrite-targeting GABA neurons by comparing their function to soma-
targeting neurons that do not express Kirrel3. Regardless of outcome, our results are expected
advance our understanding of GABA neuron activity in learning and memory and could provide a
new framework for studying GABA neurons that share synaptic connectivity genes.

## Key facts

- **NIH application ID:** 10861927
- **Project number:** 5R01MH134515-02
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** JAMES Gerard HEYS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $573,612
- **Award type:** 5
- **Project period:** 2023-06-15 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10861927

## Citation

> US National Institutes of Health, RePORTER application 10861927, Inhibitory regulation of hippocampal CA3 neuron activity, learning, and memory (5R01MH134515-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10861927. Licensed CC0.

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