Ethanol modulation of striatal complex disinhibition

Abstract

The brain dynamically interacts with the environment to ensure organism survival. Underlying this dynamism are plastic changes at synapses in a brain region known as the striatal complex that encodes the motivation to seek, and the motor skills required to obtain, rewards. Historically, work in the striatal complex has largely focused on synaptic changes at excitatory synapses. This is despite the ability for the major drug of abuse ethanol to alter both excitatory and inhibitory signaling in the striatal complex to foster alcohol use disorders. Using whole-cell electrophysiology in conjunction with ex vivo optogenetics and a variety of ethanol exposure models, I tested the effects of ethanol on the induction and maintenance of plastic changes at inhibitory synapses in the striatal complex. The work presented in this dissertation is the first to demonstrate that acute and chronic ethanol exposure in mice is capable of producing and enhancing long lasting inhibitory synaptic changes as well as altering the population activity of inhibitory interneurons. Through this work, I identify novel molecular targets to combat alcoholism and provide a clear path forward for future work in the field.