# Molecular mechanism of synapse assembly and function

> **NIH NIH R01** · BROWN UNIVERSITY · 2020 · $345,500

## Abstract

The strength of synaptic connections plays a critical role in determining information flow within
neural circuits and establishing how circuits can be modified in response to changing inputs. A
key parameter of synaptic strength is the probability of neurotransmitter release from the
presynaptic neuron. Neurotransmitter release depends on localized calcium influx triggering
fusion of molecularly primed synaptic vesicles at specialized domains of presynaptic terminals
called active zones. We and others have found that conserved proteins of the active zone
cytomatrix regulate key determinants of release probability, including the number of release-
ready synaptic vesicles, calcium channels clustering, and the spatial coupling of vesicles and
channels. Presynaptic release properties vary considerably even between neighboring AZs of
the same neuron. Yet, how proteins of the conserved AZ cytomatrix act locally to generate a
diversity of synaptic strengths is not understood. Emerging observations, including our own
preliminary data, indicate that AZ cytomatrix proteins are differentially deployed at functionally
distinct synapses, suggesting a flexible strategy for achieving functional diversity. Here, we build
on our advances in understanding local determinants of synaptic function to elucidate how
active zones are organized to achieve synapse-specific neurotransmitter release properties
(Aim 1), how synapses are reorganized during plasticity (Aim 2), and how functional
heterogeneity interacts with plasticity to support circuit function in response to changing inputs
(Aim 3).

## Key facts

- **NIH application ID:** 9838822
- **Project number:** 5R01NS078179-07
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** Kathaleen M O'Connor-Giles
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $345,500
- **Award type:** 5
- **Project period:** 2013-05-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9838822

## Citation

> US National Institutes of Health, RePORTER application 9838822, Molecular mechanism of synapse assembly and function (5R01NS078179-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9838822. Licensed CC0.

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