Anterior cingulate cortex activation of claustrum projection neuron subtypes is enhanced by alcohol.

Cognitive impairment is a major component of Alcohol Use Disorder. Optimal cognitive performance requires anterior cingulate input activation of the claustrum, a subcortical nucleus that orchestrates cortical activity. Yet the impact of chronic alcohol exposure on the ability for the anterior cingulate cortex to drive activity of claustrum projection neuron subtypes is unknown. In adult male and female mice, we found that the majority of non-burst firing Type 1 claustrum projection neurons did not express the vesicular glutamate transporter 2 (VGLUT2), while the majority of burst firing Type 2 projection neurons were VGLUT2-expressing. Following chronic intermittent vaporized ethanol exposure (CIE), we found that all claustrum neuron types exhibited increased responsivity to anterior cingulate cortex input activation. In Type 1 and VGLUT2-non-expressing neurons this was associated with increased postsynaptic membrane excitability. In contrast, Type 2 and VGLUT2-expressing projection neurons exhibited increased responsivity to anterior cingulate cortex input due to strengthened pre- and post-synaptic transmission mechanisms. Altogether, we uncovered a hyper-excitatory drive of the claustrum by the anterior cingulate cortex following chronic alcohol exposure. The data provide a foundational resource for the complex effects of chronic alcohol exposure on the claustrum, a critical cognitive control nucleus.