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Perineuronal Net and Inhibitory Synapse Remodeling on Striatal Fast-Spiking Interneurons by Chronic Alcohol Exposure
Michael S Patton1, Samuel H Sheats1, Andreas B Wulff1
1Department of Pharmacology and Physiology, University of Maryland School of Medicine, Baltimore, Maryland.
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.
