Perineuronal Net and Inhibitory Synapse Remodeling on Striatal Fast-Spiking Interneurons by Chronic Alcohol Exposure.

BACKGROUND

Alcohol use disorder is characterized by persistent drinking in the face of negative consequences. Such inflexible drinking requires dorsolateral striatum fast-spiking interneurons, which comprise approximately 1% of all striatal neurons. How chronic ethanol exposure affects fast-spiking interneuron physiology is poorly understood.

METHODS

We exposed adult male and female mice to chronic intermittent ethanol and examined synaptic transmission onto dorsolateral striatum fast-spiking interneurons.

RESULTS

We discovered that chronic ethanol exposure induced a dramatic loss of GABAergic (gamma-aminobutyric acidergic), but not glutamatergic, synapses onto dorsolateral striatum fast-spiking interneuron somata and proximal dendrites where perineuronal nets (PNNs), a subdivision of the extracellular matrix, are enriched. We found that chronic ethanol exposure degraded these PNNs and that enzymatically degrading PNNs similarly reduced GABAergic transmission onto dorsolateral striatum fast-spiking interneurons. Modeling the effect of alcohol, we found that silencing extrinsic GABAergic projections to the dorsolateral striatum increased voluntary ethanol consumption.

CONCLUSIONS

These data suggest that chronic alcohol exposure remodels PNNs and inhibitory synapses on fast-spiking interneurons to facilitate alcohol drinking.