# Defining the Role of D1 and D2 Medium Spiny Neurons in Relapse to Cocaine Seeking

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

## Abstract

Project Summary
Learned associations between environmental contexts and experience are the basis of decision-making and
allow organisms to guide behavior towards advantageous outcomes. Dysfunction in the neuronal processes
that regulate these associations, especially in the nucleus accumbens (NAc), is a critical factor in the pathology
of addiction. The NAc is a heterogeneous region primarily composed of two opposing cell types: D1 and D2
medium spiny projection neurons (MSNs). Optogenetic stimulation of these cells results in divergent behavioral
outputs; thus, it is important to study these populations in isolation to understand the cell-type specific signals
that underlie NAc-mediated learning processes. Under the primary mentorship of Dr. Eric Nestler and Dr. Paul
Kenny at Icahn School of Medicine at Mount Sinai in New York, the Pathway to Independence Award will
provide the opportunity to build on my expertise in cocaine self-administration and synaptic function while
simultaneously developing my training and expertise in in vivo calcium imaging and optogenetics. In the
mentored K-phase of this grant fiber photometry calcium imaging will be paired with cocaine self-administration
in transgenic mouse lines that express Cre-recombinase in D1 or D2 MSN populations. These mice allow for
cell-type specific expression of molecular targets, such as calcium indicators (GCaMP6f) and opsins (ChR2;
NpHR). By expressing GCaMP6f in D1 or D2 MSNs, the temporally specific signals that mediate cue-induced
cocaine seeking will be determined. Further, optogenetic stimulation and inhibition will allow for direct
manipulation of these cells and the associated seeking behavior. The innovative combination of these tools will
enable the mapping of how D1 and D2 MSNs encode cue information and concurrently establish causality. In
the independent phase (R00), these cutting-edge techniques will be combined with the inducible ArcCreERT2
mice which express constructs (GCaMP6f/Opsins) selectively in cells that are activated by environmental
stimuli during a temporally specific window. This will allow for the recording and manipulation of neuronal
ensembles that are activated by cocaine or cocaine-paired cues to determine their role in drug seeking.
Together, these data will elucidate the underlying neural processes that control associative learning and how
cocaine exposure dysregulates MSN signaling to drive relapse following abstinence, which will expand our
basic understanding of addiction and may lead to the development of novel therapeutic avenues. In summary,
the research proposed in this Pathway to Independence Award will elucidate the neural mechanisms involved
in addiction while simultaneously preparing me to develop a fully independent research program capable of
integrating a wide range of circuit based and behavioral approaches to dissect the neurobiology of addiction.
.

## Key facts

- **NIH application ID:** 9873015
- **Project number:** 5R00DA042111-05
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Erin Calipari
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $249,000
- **Award type:** 5
- **Project period:** 2018-03-15 → 2021-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9873015

## Citation

> US National Institutes of Health, RePORTER application 9873015, Defining the Role of D1 and D2 Medium Spiny Neurons in Relapse to Cocaine Seeking (5R00DA042111-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9873015. Licensed CC0.

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