PREFRONTAL NEURAL SIGNATURES OF ALCOHOL USE ACROSS DEPENDENCE AND WITHDRAWAL

The combined effects of heavy alcohol use and stress can act synergistically on neural circuits responsible for executive function control. The goals of our study were to characterize neuronal activity in the medial prefrontal cortex (mPFC) during alcohol seeking and consumption in head-fixed awake mice; identify how activity is altered during chronic alcohol and stress exposure and withdrawal; compare these neural dynamics to those observed during sucrose consumption as a natural reward. Twelve C57BL/6 mice were trained to drink 15% ethanol in their homecage before head-fixed pavlovian drinking for either 15% ethanol or 8% sucrose with distinct cues. Mice then underwent four cycles of alternating chronic intermittent ethanol (CIE) vapor exposure (1 week) and repeated forced swim stress combined with homecage drinking (1 week), to drive high alcohol consumption. Neuropixel recordings from the mPFC were performed in head-fixed awake mice throughout this experimental paradigm in each state (pre-CIE, post-CIE, post-stress, withdrawal) for cued alcohol or sucrose consumption. Preliminary analysis revealed significant changes of neuronal firing rates time-locked to lick and cue events. Across the paradigm, CIE exposure and withdrawal were associated with a reduction in the number of active single-neuron clusters from baseline to withdrawal (mean ± SEM: 92 ± 9 to 50 ±13), together with altered neuronal firing patterns of neuron activity and decreased Z-scores around lick events. In summary, our findings provide insight into mPFC neural dynamics during alcohol-induced neuroadaptations, reflecting a potential disruption in reward-related neural circuits function during the progression of alcohol use disorder and withdrawal.