Examination Date

Spring 4-6-2026

Degree

Dissertation

Degree Program

Cell Biology and Anatomy

Examination Committee

Michael Salling, Tiffany Wills, Deidre Devier, Sonia Gasparini, Nicholas Gilpin

Abstract

One of the most direct and preventable predictors of alcohol use disorder (AUD) is heavy drinking at an early age. Early alcohol consumption is hazardous as the prefrontal cortex (PFC) is actively developing. Many of the effects of early adolescent alcohol use can be attributed to alcohol’s interactions with the PFC, yet the neuroadaptations are poorly understood.

Previous work in mice has shown that intermittent adolescent alcohol (IA EtOH) results in excitability changes in prelimbic PFC pyramidal neurons. To elucidate the changes in these populations after IA EtOH, we employed a retrograde viral approach with ex-vivo whole cell patch-clamp electrophysiology in PFC projections to the nucleus accumbens (NAc), mediodorsal thalamus (MdT), and contralateral PFC. We observed changes in PFC-MdT including increased intrinsic excitability, decreased excitatory neurotransmission, and decreased hyperpolarization-activated cation current (Ih). These changes were only transient in females but persisted in males after 10 days of abstinence. These neuroadaptations were only observed after early adolescence alcohol, with no changes following late adolescence or adult alcohol.

Given the role that the PFC plays in attention and impulsivity, we aimed to characterize cognitive changes following early adolescent alcohol by using the 5-choice serial reaction timed task (5-CSRTT) and the 5-choice continuous performance task (5-CCPT). Three separate alcohol paradigms were used: escalating concentration 2-bottle choice (2-BC), 15% 2-BC, and chronic intermittent alcohol vapor. Following exposure, mice were trained in these behaviors and tested in adulthood. Our findings were inconsistent, with no clear alcohol effect being identified in the behaviors.

To validate the use of 5-CSRTT and 5-CCPT in mice to assess these aspects of cognition we used Gi DREADD to inhibit the activity of the PFC, and its projections to the MdT and dorsomedial striatum (DMS) via a dual virus strategy. No significant effect was observed on performance following DREADD ligand administration. However, across groups we saw a potential sex difference in decreased female performance in the early stages of the 5-CSRTT.

These studies show that despite a clear neuroadaptation taking place in attention and impulsivity circuitry after adolescent alcohol use, we were unable to find significant alterations to the behavior.

Additional Files
Mejia Gomez, Hernan - Dissertation Report Form.pdf (115 kB)
Dissertation Report Form
Download

Available for download on Friday, January 15, 2027

Share

COinS