# The role of axonal guidance genes in the regulation of dopamine-mediated behaviors and synaptic connectivity

> **NIH NIH F31** · UNIVERSITY OF WASHINGTON · 2021 · $40,936

## Abstract

Project Summary/Abstract:
Netrin-1 signaling through the netrin receptor deleted in colorectal cancer (Dcc) serves a critical role in neural
circuit development by promoting growth cone motility, axonal branching, and synaptogenesis. Emerging
evidence now suggests secreted netrins play an additional role in maintaining excitatory synaptic connections in
the adult brain. While netrin-1 is highly expressed during neurodevelopment, this expression decreases globally
after central nervous system (CNS) formation. Interestingly, neurons of the ventral tegmental area (VTA)
maintain high expression of both Netrin-1 and Dcc in adult mice. To date, the function of netrin-1 and netrin
receptors in VTA neurons of the adult CNS remains unknown. I hypothesize that Netrin-1 plays a fundamental
role in regulating synaptic connectivity in the adult VTA, and alterations in the expression levels of the Ntn1 gene
will result in disease relevant dysregulation of dopaminergic neuron connectivity and measurable changes in
dopamine-mediated behaviors. To test this, I propose to 1) assess synaptic contribution of Netrin-1 in the VTA
and 2) the behavioral impact of cell-type specific genetic disruption of Ntn1. Determining the function of Netrin-
1 in adult neurons will not only shed light on the molecular mechanisms responsible for regulating excitatory and
inhibitory synaptic connectivity in the midbrain dopamine system, and will contribute to our understanding of how
alterations in dopamine circuitry may contribute to psychiatric dysfunction.

## Key facts

- **NIH application ID:** 10381947
- **Project number:** 1F31MH126489-01A1
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Marcella Cline
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $40,936
- **Award type:** 1
- **Project period:** 2021-09-01 → 2022-08-19

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10381947

## Citation

> US National Institutes of Health, RePORTER application 10381947, The role of axonal guidance genes in the regulation of dopamine-mediated behaviors and synaptic connectivity (1F31MH126489-01A1). Retrieved via AI Analytics 2026-06-02 from https://api.ai-analytics.org/grant/nih/10381947. Licensed CC0.

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