Chronic alcohol disrupts premotor cortex intrinsic excitability and transmission.

Alcohol dependence induced alterations to decision-making are hypothesized to occur in part through long-lasting changes to cortical function. Animal models of chronic alcohol exposure have been used to identify alcohol-related changes to the activity and intrinsic function of cortical neurons, but the extent of such changes across involved cortical circuits is unclear. The secondary or premotor cortex (M2), which is necessary for goal-directed decision-making, shows aberrant in vivo activity during decision-making following chronic alcohol exposure, and targeting M2 activity can restore appropriate decision-making. Here we investigate whether chronic alcohol exposure alters the intrinsic properties and spontaneous transmission of M2 pyramidal neurons in male and female mice. Using a well-validated model of alcohol dependence, chronic intermittent ethanol exposure and repeated withdrawal (CIE), we find that prior CIE exposure reduced intrinsic excitability of M2 pyramidal neurons and altered glutamatergic, but not GABAergic transmission. One to two weeks into withdrawal, M2 neurons from CIE-exposed mice showed a decrease in intrinsic excitability that recovered with additional time in withdrawal. Prior CIE exposure also altered excitatory, but not inhibitory transmission within M2. Early in withdrawal there was an increase in the frequency of excitatory transmission. This change showed adaptation; with additional time in alcohol withdrawal we observed restored frequency but increased amplitude of M2 excitatory transmission. Together, this suggests that chronic alcohol exposure and withdrawal alters M2 neuron function and induces increases in excitatory modulation of M2 circuits.