# Defining the role of cortical circuit dynamics in learning and addiction

> **NIH NIH R00** · VANDERBILT UNIVERSITY · 2020 · $249,000

## Abstract

Project Summary/Abstract
The ability to update strategies as contingencies change, or cognitive flexibility, is a fundamental behavioral
process that allows for maximizing positive, while minimizing aversive, outcomes. This process is critical for
survival, and its dysregulation is a hallmark of a number neuropsychiatric disorders including addiction. For
example, cocaine addicts have a slowed ability to learn new associations, and also make risky choices despite
environmental cues indicating that more advantageous choices are available. These deficits are similar to those
seen in patients with damage to prefrontal cortical areas, and imagining studies in cocaine addicts also suggests
that cocaine-induced plasticity in medial prefrontal cortex (mPFC) may be involved. While hypotheses as to the
circuit basis of cocaine-induced cognitive deficits have been generated from clinical studies, in many cases we
lack direct, mechanistic preclinical data verifying these hypotheses. In our preliminary studies in rats we have
identified two projection-defined subpopulations in the mPFC, cells that project to the nucleus accumbens or
those that project to the periaqueductal gray area, which divergently encode positive and negative stimuli. We
hypothesize that these populations are involved in cognitive flexibility, and its dysregulation by cocaine. The
experiments put forth in this proposal will systematically test this hypothesis by combining single-cell calcium
imaging, to record endogenous activity, and optogenetics, to manipulate activity, with intravenous cocaine self-
administration. The cutting-edge technologies employed in this proposal will allow us to test the novel hypothesis
that specific subpopulations in the mPFC are critically involved in fundamental behavioral control, cognitive
flexibility, and cocaine-induced deficits in these processes. A successful outcome of this proposal will facilitate
my transition to an independent academic position, while advancing our understanding of the circuit basis of
cocaine addiction.

## Key facts

- **NIH application ID:** 10057463
- **Project number:** 4R00DA045103-03
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Cody Siciliano
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $249,000
- **Award type:** 4N
- **Project period:** 2020-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10057463

## Citation

> US National Institutes of Health, RePORTER application 10057463, Defining the role of cortical circuit dynamics in learning and addiction (4R00DA045103-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10057463. Licensed CC0.

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