# Synaptotagmin 7: A compartmentalized molecule for presynaptic short term plasticity

> **NIH NIH F31** · NORTHWESTERN UNIVERSITY · 2024 · $44,187

## Abstract

Summary/Abstract
The hippocampal mossy fiber (MF) synapse exhibits robust short term presynaptic plasticity that is responsible
for gating the flow of information into the CA3 region. MF axons make synapses with both CA3 pyramidal cells
(PCs) and stratum lucidum interneurons (SLINs), producing both direct excitation and feedforward inhibition
onto the local network. The properties of these synaptic connections have divergent phenotypes with MF-PC
synapses showing facilitation and the MF-SLIN synapse depressing during a burst of granule cell activity. This
results in a net effect of reduced inhibition and increased excitation during bursts of high frequency presynaptic
firing that causes suprathreshold activation of CA3 PCs. Despite a large body of research on these synaptic
mechanisms, it is not clear what underlies this divergent synaptic behavior of synapses formed by the same
axon and in some cases by different compartments of the same presynaptic terminal. The goal of this
fellowship is to determine if the high affinity Ca2+ sensor synaptotagmin 7 (Syt7), is responsible for creating this
high pass filter in the area CA3. To address this question I will utilize a newly created conditional knockout
mouse line where Syt7 is lost in MF presynaptic terminals. I will determine if Syt7 demonstrates
compartmentalized activity at MF to PC and MF to SLIN connections, and thus constitutes the molecular
mechanism for this circuit's behavior. Using genetic replacement approaches I will determine whether the C2
Ca2+ binding domains are necessary to explain the function of Syt7 in MF synapses. Furthermore, using high
resolution biochemical and microscopy approaches I will determine the subcellular location of Syt7 in MF
synapses to understand how the protein’s localization informs its function. Identifying the presynaptic
mechanisms responsible for information transfer will allow future work to directly test the molecular processes
underlying complex hippocampal-dependent behaviors.

## Key facts

- **NIH application ID:** 11066274
- **Project number:** 1F31MH136704-01A1
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Matthew Barraza
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $44,187
- **Award type:** 1
- **Project period:** 2024-11-01 → 2025-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11066274

## Citation

> US National Institutes of Health, RePORTER application 11066274, Synaptotagmin 7: A compartmentalized molecule for presynaptic short term plasticity (1F31MH136704-01A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/11066274. Licensed CC0.

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