# Investigating How Alcohol Withdrawal Dysregulates 'Reward' and 'Aversion' Neurons in the Basolateral Amygdala

> **NIH NIH F31** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2022 · $46,752

## Abstract

The basolateral amygdala (BLA) is critical to the development of alcohol use disorder (AUD). Its unique
position within reward- and aversion-related circuitry allows it to regulate alcohol intake and withdrawal-induced
anxiety. Glutamatergic pyramidal neurons drive these behavioral responses such that higher pyramidal neuron
excitability facilitates anxiety and reward-seeking. Pyramidal neurons receive glutamatergic inputs from midline
structures like the medial prefrontal cortex through the stria terminalis (ST) and more lateral cortical areas send
glutamatergic inputs through the external capsule (EC). GABAergic lateral paracapsular cells (LPCs) and
‘local’ interneurons regulate pyramidal neurons. The goal of my project is to examine how chronic intermittent
ethanol and withdrawal (CIE/WD) dysregulates BLA neurons projecting to reward and aversion-related regions
to understand the mechanisms driving increased alcohol intake. The nucleus accumbens (NAC) is involved in
reward-seeking while the bed nucleus of the stria terminalis (BNST) regulates anxiety. Therefore, my project
will use BLA-NAC neurons as ‘reward’ neurons and BLA-BNST neurons as ‘aversion’ neurons. Our laboratory
has shown that WD increases glutamatergic function through pre- and postsynaptic mechanisms at ST inputs
and EC-BLA synapses, respectively. My preliminary data reveal that WD increases glutamate release from ST
inputs onto BLA-BNST neurons regardless of sex, whereas the WD-mediated increase in postsynaptic function
at EC-BLA synapses is both projection- and sex-dependent. My preliminary data also indicate that WD alters
the excitability of BLA-NAC and BLA-BNST neurons when GABAergic transmission is blocked. In BLA-NAC
neurons, females have higher basal excitability and only males increase excitability after CIE/WD. In BLA-
BNST neurons, WD increases excitability, regardless of sex. Blocking glutamatergic and GABAergic
transmission abolished the increase in excitability, emphasizing the role of glutamatergic transmission in WD-
mediated hyperexcitability. This proposal will continue to investigate how WD impacts ‘reward’ and ‘aversion’
BLA neurons. Specific Aim 1 will employ electrophysiology and retrograde labeling to examine GABAergic
function in synapses with BLA-NAC and BLA-BNST neurons. Laboratory data reveal that WD suppresses LPC
GABA release and postsynaptic GABAergic function in ‘local’ interneuron synapses. Moreover, reduced LPC
GABA release is unique to males. Specific Aim 1 will also examine structural plasticity in GABAergic synapses
with BLA-NAC and BLA-BNST neurons using immunohistochemistry, confocal microscopy, and retrograde
labeling. Specific Aim 2 will combine behavioral approaches and chemogenetics to inhibit specific BLA circuits
and evaluate their role in post-CIE alcohol intake. These experiments will establish that ‘reward’ and ‘aversion’
BLA neurons undergo distinct neurophysiological and structural changes, leading to increased alcohol intake
afte...

## Key facts

- **NIH application ID:** 10536418
- **Project number:** 1F31AA029933-01A1
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Michaela Price
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $46,752
- **Award type:** 1
- **Project period:** 2022-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10536418

## Citation

> US National Institutes of Health, RePORTER application 10536418, Investigating How Alcohol Withdrawal Dysregulates 'Reward' and 'Aversion' Neurons in the Basolateral Amygdala (1F31AA029933-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10536418. Licensed CC0.

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