# Neurotransmitter Corelease

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $376,618

## Abstract

Accumulating evidence shows that many neurons release two classical neurotransmitters, but
fundamental questions remain about the cellular basis for corelease, with important implications for its
physiological role. In this proposal, we use the vesicular neurotransmitter transporters to elucidate the
mechanisms involved in corelease. In previous work, we showed that glutamate corelease by midbrain
dopamine neurons serves two distinct roles, one in vesicle filling with dopamine and the other as an independent
signal. Although the effects on vesicle filling require colocalization of the vesicular monoamine transporter
VMAT2 and vesicular glutamate transporter VGLUT2 on the same synaptic vesicles, anatomy has suggested
some segregation as well, but with unclear physiological consequences.
We now find that dopamine neurons release glutamate and dopamine with different properties. Release
of the two transmitters differs in short-term depression and depends on different presynaptic Ca++ channels.
Synaptic vesicles belong to pools that differ in response to stimulation but these differences have been attributed
to extrinsic factors such as cytoskeletal association. We now show that they also differ in composition because
they contain different transmitters and release them with different properties. Through this mechanism, a single
neuron can deconvolve its input into two distinct outputs. The long-term objectives of this project are to elucidate
the cellular and molecular basis for neurotransmitter corelease and determine its role in information processing.
The strategy is to use the vesicular transporters to characterize the different vesicle populations. Specifically,
we will
1) compare monoamine and glutamate release by imaging VMAT2 and VGLUT2 in live neurons;
2) determine how VMAT2 and VGLUT2 target to distinct vesicle populations;
3) characterize the composition of monoamine and glutamate SVs by proteomics.
The results will provide basic information about the organization of neurons, with direct relevance for corelease
by other cells, but also for release by all neurons.

## Key facts

- **NIH application ID:** 10168663
- **Project number:** 5R01NS103938-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** ROBERT H EDWARDS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $376,618
- **Award type:** 5
- **Project period:** 2017-09-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10168663

## Citation

> US National Institutes of Health, RePORTER application 10168663, Neurotransmitter Corelease (5R01NS103938-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10168663. Licensed CC0.

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