Adolescent binge drinking leads to long-lasting changes in cortical microcircuits in mice

Abstract

Adolescent drug consumption has increased risks to the individual compared to consumption in adulthood, due to the likelihood of long-term and permanent behavioral and neurological adaptations. However, little is known about how adolescent alcohol consumption influences the maturation and trajectory of cortical circuit development. Here, we explore the consequences of adolescent binge drinking on somatostatin (SST) neuronal function in the prelimbic (PL) cortex. We find that adolescent drinking-in-the-dark (DID) produces sex-dependent increases in intrinsic excitability of SST neurons, persisting well into adulthood. We found a complementary reduction in pyramidal neuron excitability immediately after binge drinking; however, this hypoexcitability rebounded towards increased pyramidal neuron activity in adulthood in females, suggesting long-term homeostatic adaptations in this circuit. Together, this suggests that binge drinking during key developmental timepoints leads to permanent changes in PL microcircuitry function, which may have broad behavioral implications.

Parvalbumin interneuron mGlu5receptors govern sex differences in prefrontal cortex physiology and binge drinking

“…Even in the closely related somatostatin-expressing interneurons, we and others found minimal evidence for sex differences in basal properties [42,[89][90][91] or in mGlu receptor signaling [29,92].…”

“…However, mGlu 5 receptors are one of the most widely expressed GPCRs in the CNS but most cell types do not express overt physiological sex differences. Even in the closely related somatostatin-expressing interneurons, we and others found minimal evidence for sex differences in basal properties [42,86–88] or in mGlu receptor signaling [29,89]. These findings beg the question, what factors make PV-INs sensitive to sex-dependent mGlu receptor signaling?…”

Moderate Alcohol Consumption Induces Lasting Impacts on Prefrontal Cortical Signaling in Mice

“…Electrophysiology was conducted between 9-12 months of age (+/-2 weeks; corresponding to about 6 months following the cessation of alcohol consumption) similar to our previously published work Sicher et al, 2023). Mice were exposed to an isoflurane chamber for deep anesthetization, the brain was quickly extracted and processed according to the N-methyl-D-glucamine (NMDG) protective recovery method (Ting et al, 2014).…”