# Dopaminergic regulation of prefrontal activity patterns during behavior

> **NIH NIH K08** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2022 · $194,728

## Abstract

PROJECT SUMMARY / ABSTRACT
Dopaminergic projections from ventral tegmental area (VTA) to medial prefrontal cortex (mPFC), underlie
critical functions disrupted across many neuropsychiatric conditions. However, the circuit-level mechanisms by
which prefrontal dopamine modulates specific behaviors remain poorly understood. The scientific objective of
this project is to determine how particular patterns of neural activity relate to distinct behavioral states and how
prefrontal dopamine alters these patterns to influence behavior.
My preliminary studies have shown that activating dopamine D2 receptors (D2Rs) in prefrontal brain slices
enhances a positively correlated activity state. D2Rs are preferentially activated by the high dopamine state
induced by phasic bursting of VTA neurons. I find that phasic, but not tonic stimulation of VTA-mPFC
projections elicits active coping in the tail suspension test (TST). Finally, I show using in vivo imaging of activity
that correlations between neurons fall over the course of active coping bouts, culminating in a transition to
immobility. These data suggest the main hypothesis of the proposed project, that passive coping results from a
breakdown of correlated activity and active coping is maintained by D2R-driven increases in correlations.
In aim 1, I will employ optogenetics to further define how phasic and tonic patterns of activity in VTA-mPFC
afferents influence different behaviors. In aim 2, I will use head-mounted miniscopes to confirm and expand
the initial finding that correlations degrade during struggling, imaging activity in D1 and D2R expressing
subnetworks. In aim 3, I will directly alter activity in elements of VTA-mPFC circuitry to establish causal
relationships between dopamine and circuit activity-behavior relationships. These results will establish a
foundation for my future work as this award allows me to start an independent laboratory.
In addition to conducting the proposed studies, I will be mentored towards independence by Dr. Vikaas Sohal
in whose laboratory this work will be accomplished. My scientific development will be aided by specific aspects
of the mentoring plan, including coursework, workshops, journal clubs and presentations at conferences. As a
physician, I will continue to expand my expertise in treating depression by learning cutting-edge techniques to
modulate activity in the brain. By the completion of the award, I will have obtained a professorship and
successfully applied for an R01 grant to launch an independent research program in neural circuits related to
mood disorders.

## Key facts

- **NIH application ID:** 10460641
- **Project number:** 5K08MH116125-06
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Scott Allen Wilke
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $194,728
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10460641

## Citation

> US National Institutes of Health, RePORTER application 10460641, Dopaminergic regulation of prefrontal activity patterns during behavior (5K08MH116125-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10460641. Licensed CC0.

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