# Dynamic regulation of synaptic Ca2+ channel organization

> **NIH NIH F31** · BROWN UNIVERSITY · 2021 · $46,036

## Abstract

PROJECT SUMMARY
Presynaptic Ca2+ drives neurotransmission at the trillions of chemical synapses that mediate most
communication in the nervous system. Ca2+ influx through voltage-gated Ca2+ channels raises localized
intracellular Ca2+, which binds to Ca2+ sensors on synaptic vesicle fusion machinery, resulting in vesicle fusion
and release of neurotransmitter at specialized areas of synapses called active zones. The abundance and
precise location of Ca2+ channels have a profound impact on synapse function, yet the relationship between
Ca2+ channel organization and synaptic function has been difficult to study. The Drosophila neuromuscular
junction (NMJ) provides an attractive model for studying this question at endogenous synapses by allowing us
to compare Ca2+ channel composition, organization and dynamic regulation at two related motor neuron
subtypes with very different neurotransmitter release properties. In Aim 1, I will investigate the role of Ca2+
channel auxiliary subunits and nanoscale organization in establishing synapse-specific release properties
using CRISPR gene editing, super-resolution imaging, and electron microscopy.
Synapses must be reliable, but also malleable to adapt their responses to a dynamic environment. Presynaptic
homeostatic potentiation (PHP) is a conserved mechanism for maintaining effective neural communication
within a dynamic range through an increase in synaptic probability of release. Previous work from our lab has
shown that manipulations to induce PHP result in a rapid recruitment of voltage-gated Ca2+ channels to active
zones, but how new channels are trafficked to and organized at active zones remains unknown. In Aim 2, I will
use genetics and pharmacology to investigate the cellular mechanisms by which Ca2+ channels are trafficked,
inserted in the membrane, and clustered to facilitate changes in release properties during homeostatic
plasticity.
This research will reveal how Ca2+ channels are differentially and dynamically regulated to achieve and
maintain synapse-specific release properties, and advance our understanding of communication in the nervous
system.
By completing these aims, the applicant will gain scientific and technical expertise in cellular neurobiology,
neurogenetics, CRISPR gene editing, super-resolution imaging, and electrophysiology. Through a
comprehensive training plan, this fellowship will support the professional development of the applicant in robust
experimental design and data analysis; written and oral scientific communication; and effective and inclusive
mentoring. Successful completion of the research and training goals are fully supported by the interactive and
supportive institutional environment of Brown University and in the Neuroscience Graduate Program, and will
prepare the applicant for the next steps towards an independent scientific career.

## Key facts

- **NIH application ID:** 10234412
- **Project number:** 1F31NS122424-01
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** Audrey Taylor Medeiros
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $46,036
- **Award type:** 1
- **Project period:** 2021-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10234412

## Citation

> US National Institutes of Health, RePORTER application 10234412, Dynamic regulation of synaptic Ca2+ channel organization (1F31NS122424-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10234412. Licensed CC0.

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