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

Area of Science:

• Neuroscience
• Addiction Research
• Cellular Biology

Background:

• Alcohol use disorder involves persistent drinking despite negative consequences.
• Dorsolateral striatum fast-spiking interneurons are crucial for inflexible drinking behaviors.
• The impact of chronic ethanol on these specific interneurons remains largely unknown.

Purpose of the Study:

• To investigate how chronic ethanol exposure alters the physiology of dorsolateral striatum fast-spiking interneurons.
• To understand the role of perineuronal nets in alcohol-induced neural changes.

Main Methods:

• Adult male and female mice were exposed to chronic intermittent ethanol.
• Synaptic transmission onto dorsolateral striatum fast-spiking interneurons was analyzed.
• Perineuronal nets were enzymatically degraded to assess their role.

Main Results:

• Chronic ethanol exposure led to a significant loss of GABAergic synapses on fast-spiking interneurons.
• Degradation of perineuronal nets was observed following chronic ethanol exposure.
• Enzymatic degradation of perineuronal nets mimicked the reduction in GABAergic transmission.
• Silencing GABAergic projections increased voluntary ethanol consumption in models.

Conclusions:

• Chronic alcohol exposure remodels perineuronal nets and inhibitory synapses.
• These alterations on fast-spiking interneurons contribute to the facilitation of alcohol drinking.
• Findings provide insights into the neurobiological mechanisms underlying alcohol use disorder.