Selective impairment of spatial recognition memory and reduced frontal corticothalamic spine density following adolescent alcohol consumption

Abstract

Heavy alcohol use is common during adolescence and is associated with increased risk of alcohol use disorder and prevalence of residual cognitive deficits, especially in behaviors associated with the latently developing prefrontal cortex (PFC). A major need for advancing our understanding of this relationship is replicable and accessible preclinical behavioral batteries that can be used to disassociate the effects of adolescent alcohol on select PFC circuits. Electrophysiological evidence implicates projections from the PFC to mediodorsal thalamus (PFC-MdT) as being uniquely impacted by adolescent intermittent alcohol consumption in mice. The present study aims to evaluate if voluntary consumption of alcohol during adolescence impacts anxiety or PFC-associated spatial and recognition memory and if they are associated with morphological changes to the PFC-MdT circuit. Our results indicate that compared to water-only controls, male and female mice that voluntarily consumed alcohol during adolescence demonstrate performance deficits in the object-in-place recognition task, without affecting the novel object recognition task, Y-maze alternation, anxiety or locomotion, an outcome consistent with PFC and MdT dysfunction. Morphological assessment of PFC neurons from male and female mice following behavioral tasks found a reduction in spine density in basal and apical, but not oblique dendrites of PFC-MdT neurons. Collectively, these results implicate the PFC to MdT circuit integrity as a potential locus of the effects of adolescent alcohol on spatial recognition memory.