Alcohol disrupts long-term potentiation at hippocampus-medium spiny neuron synapses in the medial shell of the nucleus accumbens.

BACKGROUND

Chronic alcohol exposure is a major driver of alcohol use disorders (AUD), in part through its ability to induce maladaptive plasticity within neural circuits that regulate reward, motivation, and affect. Excitatory projections from the hippocampus (Hipp) to the nucleus accumbens (NAc) play a pivotal role in regulating reward-related behaviors, and this pathway serves as a key locus for establishing associations between rewarding stimuli and related contextual information. Regulation of the strength of Hipp-NAc synapses is critical for supporting these behaviors, and aberrant Hipp-NAc plasticity is associated with anhedonia and disrupted reward learning.

METHODS

To examine acute ethanol effects, we used whole-cell electrophysiology to record Hipp-NAc synaptic plasticity in acute brain slices in the presence or absence of 50mM ethanol. To examine the effects of chronic ethanol administration, mice were exposed to ethanol vapor in a 3-week chronic intermittent ethanol (CIE) paradigm. Slices from ethanol and air exposed mice were used for whole-cell electrophysiology to record Hipp-NAc synaptic plasticity.

RESULTS

Here, we demonstrate that acute ethanol application to brain slices prevents long-term potentiation (LTP) at Hipp-NAc synapses, without altering presynaptic release probability. Furthermore, chronic intermittent exposure to ethanol abolishes LTP at these synapses, even during abstinence, indicating persistent synaptic dysfunction.

CONCLUSIONS

Together, our findings demonstrate that ethanol has immediate and long-lasting effects on Hipp-NAc plasticity. Given the behavioral relevance of these synapses, this work has important implications for the mechanisms underlying ethanol-dependent effects on reward processing and negative affective states associated with AUD.