“Neural Firing Patterns Underlying Compulsive Alcohol Consumption in a Rodent Model of Genetic Risk for Alcohol Use Disorder”

Nicholas Timme, PhD

Post-Doctoral Researcher,

Indiana University – Purdue University Indianapolis

Wednesday, April 13th at 9:00 am

On Zoom

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A defining feature of compulsive drinking is continuing to drink despite negative consequences.  This behavior characterizes an advanced stage of an alcohol use disorder that is associated with poor treatment outcomes. In this presentation, I will discuss a recent experiment that examined the neurocomputational underpinnings of compulsive drinking in a rodent model of genetic risk for alcohol use disorder. Specifically, this study focused on the role played by the dorsal medial prefrontal cortex (dmPFC), a brain region involved in maladaptive decision-making in addiction. Novel advances in principal component and change point analyses were employed to dissect neural population representations of specific decision-making variables. Compulsive subjects showed weakened representations of behavioral control signals that relate to drinking within a trial, but strengthened session-wide seeking state representations that were associated with drinking engagement at the start of each drinking opportunity. Furthermore, chemogenetic-based excitation of dmPFC prevented escalation of compulsive drinking. Collectively, these data indicate that compulsive drinking is associated with alterations in dmPFC neural activity that underlie diminished behavioral control and enhanced seeking.

I obtained my bachelor’s degree from Illinois Wesleyan University in 2008, double majoring in physics and philosophy. I obtained my doctorate in physics from Indiana University in 2015, majoring in biophysics under the mentorship of John Beggs. In my graduate work, I used electrophysiology to examine the behavior of networks of neurons in vitro using information theory and statistical mechanics techniques. During my postdoc, I have been working in Chris Lapish’s laboratory at Indiana University – Purdue University Indianapolis using in vivo extracellular electrophysiology and neural population analysis techniques to study decision-making in the context of alcohol use disorder. My current experiments, supported by an NIAAA K99 award, use high-density neural probes in head-fixed mice to study the decision to consume alcohol. These experiments place an emphasis on multi-brain region interactions and drinking despite negative consequences.

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