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

Area of Science:

• Neuroscience
• Addiction Research

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 unclear.

Purpose of the Study:

• To investigate how chronic ethanol exposure affects the physiology of dorsolateral striatum fast-spiking interneurons.
• To elucidate the role of perineuronal nets and GABAergic synapses in alcohol consumption.

Main Methods:

• Utilized mouse models to study chronic ethanol exposure.
• Examined synaptic changes (GABAergic and glutamatergic) on fast-spiking interneurons.
• Assessed the impact of perineuronal net degradation on neuronal function.
• Employed computational modeling to simulate the effects of altered GABAergic signaling.

Main Results:

• Chronic ethanol exposure led to a significant loss of GABAergic synapses on dorsolateral striatum fast-spiking interneurons.
• Perineuronal nets surrounding these interneurons were degraded by chronic ethanol exposure.
• Enzymatic degradation of perineuronal nets mimicked the reduction in GABAergic transmission.
• Silencing GABAergic projections to the dorsolateral striatum increased voluntary ethanol intake in models.

Conclusions:

• Chronic alcohol exposure remodels perineuronal nets and inhibitory synapses on fast-spiking interneurons.
• These neuroadaptations facilitate continued alcohol drinking, suggesting a mechanism for alcohol use disorder.
• Targeting perineuronal nets or GABAergic signaling may offer therapeutic strategies for alcohol use disorder.