Prefrontal cortex projections to the mediodorsal thalamus are uniquely vulnerable to the effects of early adolescent alcohol consumption

Authors

• Hernan Mejia-Gomez, LSU Health Sciences Center - New OrleansFollow
• Jessica Fawcett-Patel, LSU Health Sciences Center - New Orleans
• Faith M. Maxwell, LSU Health Sciences Center - New OrleansFollow
• Grant Collins, LSU Health Sciences Center - New OrleansFollow
• Sara A. Zakris, LSU Health Sciences Center - New Orleans
• Michael C. Salling, LSU Health Sciences Center - New OrleansFollow

Document Type

Article

Publication Date

6-6-2026

Publication Title

Neuropharmacology

Abstract

A bevy of clinical and preclinical evidence has established that the prefrontal cortex (PFC) is negatively affected by heavy alcohol consumption during adolescence, yet the specific neuroadaptations to the PFC associated with adolescent alcohol are not well understood. Using a retrograde viral approach and ex vivo whole-cell patch-clamp electrophysiology, we examined the impact of adolescent alcohol consumption on neuronal excitability in specific projections from the prelimbic PFC to the contralateral PFC (PFC), nucleus accumbens (PFC), or mediodorsal thalamus (PFC). Following adolescent alcohol consumptions, we observed several electrophysiological effects specifically to PFC pyramidal neurons (PNs) including increased intrinsic excitability due to a reduction in the hyperpolarization-activated, nonselective cation current (I) and decreased excitatory synaptic neurotransmission. Many of these effects were persistent in male mice as they were observed after 10 days of abstinence in PFC PNs and were not seen when IA EtOH was initiated in adulthood or even in late adolescence. To further characterize the consequences of adolescent alcohol consumption on PFC dependent behaviors, we performed touchscreen-based operant tasks aimed at more directly assessing PFC-dependent cognition. We found that cognitive flexibility and working memory performance were not largely affected by adolescent alcohol, however, additional analyses revealed blunted task shifting and delayed response latencies. The PFC circuit has previously been implicated in response timing and attentional processes and therefore exposure to alcohol during the early adolescent window may disrupt executive function through adaptations to PFC circuitry.

First Page

1

Last Page

16

PubMed ID

42252077

Volume

298

Comments

Featured in Faculty Publications Display; September 2026

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.

Recommended Citation

Mejia-Gomez, Hernan; Fawcett-Patel, Jessica; Maxwell, Faith M.; Collins, Grant; Zakris, Sara A.; and Salling, Michael C., "Prefrontal cortex projections to the mediodorsal thalamus are uniquely vulnerable to the effects of early adolescent alcohol consumption" (2026). School of Graduate Studies Faculty Publications. 623.
https://digitalscholar.lsuhsc.edu/sogs_facpubs/623
10.1016/j.neuropharm.2026.111015