# Mitochondrial diversity as a regulator of cell- and circuit-specific functions

> **NIH NIH R01** · VIRGINIA POLYTECHNIC INST AND ST UNIV · 2024 · $400,000

## Abstract

PROJECT SUMMARY/ABSTRACT
The goal of this research proposal is to gain mechanistic insight into how the distinct mitochondrial properties of
hippocampal CA2 neurons contribute to their function in learning and memory. Area CA2 is an understudied
region of the hippocampus that has recently gained attention due to its unique capacity to encode social infor-
mation. However, the molecular mechanisms underlying the essential processes in CA2 required for its function
in social memory are unknown. This proposal builds upon our recent finding that hippocampal CA2 pyramidal
neurons have molecularly and functionally distinct mitochondria compared with neighboring CA1 neurons. Spe-
cifically, our data point to differences in mitochondrial calcium uptake and bioenergetics, which we propose con-
fer unique synaptic and circuit properties essential to CA2 function.
It remains unclear how mitochondrial diversity influences cell- and circuit-specific functions. Incomplete
knowledge of the impact of mitochondrial heterogeneity is a key obstacle impeding our understanding of mito-
chondrial function in brain health and disease. The specific aims of this grant use innovative tools to visualize
and modify molecularly distinct mitochondria to investigate the role of mitochondrial calcium uptake in driving
bioenergetics, mitochondrial localization, and plasticity in the hippocampal circuit. We propose that mitochon-
drial diversity might be a key node in the regulation of cell specific properties underlying neural function, and
may influence region-specific differences in disease pathology. Completion of this project will advance our un-
derstanding of the basic cell biological mechanisms regulating a cell type important for social memory and will
identify novel therapeutic candidates for disorders with social deficits, such as schizophrenia and autism. The
general principles learned about mitochondrial heterogeneity from this proposal will be broadly applicable to
other brain areas and organ systems.

## Key facts

- **NIH application ID:** 10892057
- **Project number:** 5R01MH124997-04
- **Recipient organization:** VIRGINIA POLYTECHNIC INST AND ST UNIV
- **Principal Investigator:** Shannon Farris
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $400,000
- **Award type:** 5
- **Project period:** 2021-09-20 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10892057

## Citation

> US National Institutes of Health, RePORTER application 10892057, Mitochondrial diversity as a regulator of cell- and circuit-specific functions (5R01MH124997-04). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10892057. Licensed CC0.

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