# Dense-Core Vesicle Circulation, Capture and Synaptic Neuropeptide Release

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $542,813

## Abstract

Project Description
 Neuropeptides and neurotrophins are packaged in dense-core vesicles (DCVs) in the soma and
released at synaptic terminals to control development, mood and numerous behaviors. Despite the importance
of neuronal DCVs, little was known about how they are delivered to terminals and release their contents at
synapses. Our GFP-based imaging studies combined with Drosophila genetics have revealed that control of
synaptic peptide stores and exocytotic release do not operate as advertised in text books. First, instead of a
one-way trip mediated by anterograde axonal transport, DCVs circulate in and out of synapses with capture
occurring during both anterograde and retrograde transport. Moreover, contrary to long-held assumptions,
capture limits the size of presynaptic neuropeptide pool. Furthermore, we have recently found that capture
efficiency is directionally controlled by activity, neuron subtype and disease-related genes. Second, preliminary
studies suggest that DCV transport appears to be adjusted for extensive innervation with many boutons (e.g.
~1000) and injury in the terminal. The latter effect is associated with intraterminal Ca2+ release, which may
potentiate synaptic function to compensate for loss of boutons induced by injury. Third, a monoamine
neuromodulator and intracellular cAMP evoke robust synaptic peptide release, with the latter displaying
mechanistic differences from release evoked by action potentials. These results suggest that, in addition to
conventional transmission evoked by electrical activity, synaptic peptide release is evoked by intracellular Ca2+
release and cAMP signaling. Here fluorescent protein imaging in Drosophila neurons addresses three
questions posed by our prior work on this project:
1. What molecular mechanisms selectively control presynaptic DCV capture and neuropeptide release?
2. How is vesicle circulation regulated to support extensive, diverse and injured terminals?
3. What is the release mechanism and physiological impact of intracellular Ca2+ and/or cAMP signaling
 evoked by injury and neuromodulators?
 These studies will yield fundamental insights into the maintenance of terminals and the regulation of
synaptic release of neuropeptides and neurotrophins. Furthermore, the proposal will show how these
processes are affected by acute injury and disease-related genes.

## Key facts

- **NIH application ID:** 9926316
- **Project number:** 5R01NS032385-24
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** EDWIN S LEVITAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $542,813
- **Award type:** 5
- **Project period:** 1995-08-04 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9926316

## Citation

> US National Institutes of Health, RePORTER application 9926316, Dense-Core Vesicle Circulation, Capture and Synaptic Neuropeptide Release (5R01NS032385-24). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9926316. Licensed CC0.

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