# Dependence-Induced Excessive Ethanol Consumption: Role of Corticostriatal Kv7 Channels

> **NIH NIH K01** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2021 · $186,095

## Abstract

ABSTRACT
This is an application for a Mentored Research Scientist Development Award (K01) to support the career
development and intensive training of Dr. Jennifer Rinker to facilitate her transition to an independent academic
investigator in the alcohol research field. The candidate is an early-stage investigator transitioning from
Postdoctoral Fellow to Assistant Professor. Dr. Rinker has extensive experience with in vivo pharmacology and
chemogenetic manipulations to study the neural circuitry involved in alcohol use disorder, but has limited
experience with slice electrophysiology and advanced molecular techniques to examine plasticity-related events.
An intense and comprehensive training, mentoring and research plan has been developed that will provide
training in advanced techniques to assess Kv7 channel involvement in alcohol dependence-induced changes in
functional plasticity. Dr. Rinker's training will be supported by a firm institutional commitment to her career
development and a strong mentoring team of leaders in the alcohol research field, each providing strategic
guidance in both the development of this proposal and mentoring as her career progresses. The proposed
research plan is a natural extension of the recent studies Dr. Rinker has been conducting in the mentor's
laboratory, but is distinguished by its examination of Kv7 channels in discrete corticostriatal circuits in modulating
the effects of dependence-induced ethanol consumption. The medial prefrontal cortex (mPFC) is a critical
structure involved in imposing inhibitory control over reward-motivated behaviors and projects to the nucleus
accumbens (NAc), an essential component of the mesolimbic reward pathway. Ethanol dependence is
associated with elevated and uncontrolled drinking and is known to alter the plasticity and physiology of mPFC
pyramidal neurons. Specifically, ethanol withdrawal results in the hyperexcitability of NAc-projecting mPFC
neurons, the underlying mechanism of which remains unknown. Kv7 channels generate the M-current that critical
regulates neuronal excitability by maintaining the membrane potential and dampening neuronal firing. These
channels have been implicated in regulating ethanol consumption in the NAc, but their role in the corticostriatal
circuits in dependent rodents remains unexplored. Thus, the overarching hypothesis of this proposal is that
dependence-induced neuroadaptations in Kv7 channels in the corticostriatal circuitry (i.e., mPFC to NAc)
drive the escalated and uncontrolled ethanol consumption in dependence. This proposal will test this
hypothesis using a multifaceted approach incorporating subcellular analysis of protein expression and analysis
of structural and functional plasticity using diolistic labeling and slice electrophysiology, respectively. Our results
demonstrating involvement of Kv7 channels in heavy drinking and dependent mice suggests that continuing
these studies will significantly advance our understanding of the cel...

## Key facts

- **NIH application ID:** 10135671
- **Project number:** 5K01AA025110-05
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Jennifer Anne Rinker
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $186,095
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10135671

## Citation

> US National Institutes of Health, RePORTER application 10135671, Dependence-Induced Excessive Ethanol Consumption: Role of Corticostriatal Kv7 Channels (5K01AA025110-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10135671. Licensed CC0.

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