Mediodorsal thalamus of alcohol-dependent mice shows genetic and physiological adaptations and alcohol-biased calcium signaling

Alcohol Use Disorder (AUD) is a significant health concern characterized by cognitive dysfunction and an inability to control alcohol intake leading to severe social and health consequences. It is crucial to uncover neuroadaptations and cellular mechanisms responsible for poor decisions surrounding alcohol drinking. Although the mediodorsal thalamus (MD) is an essential brain region for cognitive function and reward-guided choices, the effects of alcohol dependence on MD neuroadaptations and how dependence alters MD activity during choice behaviors for alcohol over natural rewards (i.e., sucrose) are not well understood. Genetic and physiological adaptations in the MD were assessed in mice treated with the chronic intermittent ethanol (CIE) exposure model of dependence, which increased alcohol intake and preference during choice sessions for water or sucrose. Results indicated that CIE exposure induced changes in transcript expression and excitability of MD neurons. Enrichment analysis of alcohol-sensitive genes revealed dysregulation of genes that control glial function and axonal myelination. Fiber photometry was used to record MD calcium signals in CIE mice during choice drinking sessions for alcohol and either water or sucrose. Results demonstrated that MD activity was elevated at the start of and after licking bouts for alcohol, water, or sucrose, although the signal for alcohol was significantly higher than signal for other solutions and this effect persisted after induction of dependence. These findings demonstrate that CIE exposure causes genetic and physiological neuroadaptations in the MD that coincide with alcohol-biased behaviors, with the MD uniquely responsive to alcohol over other solutions.