Event Title

Excessive Alcohol Consumption during Adolescence in Mice Leads to Persistent Alterations in Prefrontal Cortex Excitability and Function

Presenter Information

Samantha Regan, Oberlin College

Location

Science Center, Bent Corridor

Start Date

10-2-2015 12:00 PM

End Date

10-2-2015 1:20 PM

Poster Number

46

Abstract

Excessive alcohol use during adolescence is a major factor in the development of alcohol use disorders (AUDs). The prefrontal cortex (PFC) may be particularly vulnerable to alcohol during adolescence and evidence suggests PFC dysfunction drives aspects of compulsive behavior observed in AUDs. To better understand how excessive alcohol affects the adolescent PFC, we used ex vivo slice electrophysiology to measure PFC neuronal excitability following adolescent alcohol consumption in mice. Under an intermittent schedule, mice voluntarily consumed binge levels of alcohol, an exposure that resulted in working memory deficits on the T-maze. Concurrently, we performed whole-cell patch clamp electrophysiology on pyramidal neurons (PNs) of the PFC. PNs from binge drinking mice had a significantly hyperpolarized resting membrane potential, increased input resistance, and increased membrane time constant. Furthermore, PFC PNs demonstrated increased excitability and a reduction in voltage sag following depolarizing current steps. These findings are consistent with a reduction in hyperpolarization-activated current (Ih) known to be mediated by HCN channels in the cortex. In voltage clamp, we isolated Ih using the HCN blocker ZD7288, and found a significant reduction in ZD7288-sensitive current. Importantly, we found similar effects at 2 and 5 weeks into abstinence demonstrating that these effects persist within our window of behavioral testing. In addition, we found HCN1 KO mice show higher alcohol preference during adolescence compared to their WT littermates. Collectively, these data identify reduced Ih in the PFC as a consequence of adolescent binge drinking and suggest that it may affect working memory and alcohol preference.

Major

Neuroscience

Project Mentor(s)

Michael Salling and Neil Harrison, Anesthesiology, Columbia University Medical Center

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Oct 2nd, 12:00 PM Oct 2nd, 1:20 PM

Excessive Alcohol Consumption during Adolescence in Mice Leads to Persistent Alterations in Prefrontal Cortex Excitability and Function

Science Center, Bent Corridor

Excessive alcohol use during adolescence is a major factor in the development of alcohol use disorders (AUDs). The prefrontal cortex (PFC) may be particularly vulnerable to alcohol during adolescence and evidence suggests PFC dysfunction drives aspects of compulsive behavior observed in AUDs. To better understand how excessive alcohol affects the adolescent PFC, we used ex vivo slice electrophysiology to measure PFC neuronal excitability following adolescent alcohol consumption in mice. Under an intermittent schedule, mice voluntarily consumed binge levels of alcohol, an exposure that resulted in working memory deficits on the T-maze. Concurrently, we performed whole-cell patch clamp electrophysiology on pyramidal neurons (PNs) of the PFC. PNs from binge drinking mice had a significantly hyperpolarized resting membrane potential, increased input resistance, and increased membrane time constant. Furthermore, PFC PNs demonstrated increased excitability and a reduction in voltage sag following depolarizing current steps. These findings are consistent with a reduction in hyperpolarization-activated current (Ih) known to be mediated by HCN channels in the cortex. In voltage clamp, we isolated Ih using the HCN blocker ZD7288, and found a significant reduction in ZD7288-sensitive current. Importantly, we found similar effects at 2 and 5 weeks into abstinence demonstrating that these effects persist within our window of behavioral testing. In addition, we found HCN1 KO mice show higher alcohol preference during adolescence compared to their WT littermates. Collectively, these data identify reduced Ih in the PFC as a consequence of adolescent binge drinking and suggest that it may affect working memory and alcohol preference.