
You have already added 0 works in your ORCID record related to the merged Research product.
You have already added 0 works in your ORCID record related to the merged Research product.
<script type="text/javascript">
<!--
document.write('<div id="oa_widget"></div>');
document.write('<script type="text/javascript" src="https://beta.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=undefined&type=result"></script>');
-->
</script>
Chronic ethanol exposure alters prelimbic prefrontal cortical Fast-Spiking and Martinotti interneuron function with differential sex specificity in rat brain

Chronic ethanol exposure results in numerous neurobiological adaptations that promote deficits in medial prefrontal cortical (mPFC) function associated with blunted inhibitory control and elevated anxiety during withdrawal. Studies exploring alcohol dependence-related changes in this region have largely investigated adaptations in glutamatergic signaling, with inhibitory neurotransmission remaining relatively understudied. To address this, we used biochemical and electrophysiological methods to evaluate the effects of ethanol on the activity of deep-layer prelimbic mPFC Fast-Spiking (FS) and Martinotti interneurons after chronic ethanol exposure in male and female rats. We report that chronic alcohol exposure significantly impairs FS neuron excitability in both males and females. Interestingly, we observed a marked sex difference in the baseline activity of Martinotti cells that furthermore displayed differential sex-specific responses to alcohol exposure. In addition, alcohol effects on Martinotti neuron excitability negatively correlated with hyperpolarization-activated currents mediated by hyperpolarization-activated cyclic nucleotide gated (HCN) channels, indicative of a causal relationship. Analysis of HCN1 protein expression also revealed a substantial sex difference, although no effect of ethanol on HCN1 protein expression was observed. Taken together, these findings further elucidate the complex adaptations that occur in the mPFC after chronic ethanol exposure and reveal fundamental differences in interneuron activity between sexes. Furthermore, this disparity may reflect innate differences in intracortical microcircuit function between male and female rats, and offers a tenable circuit-level explanation for sex-dependent behavioral responses to alcohol.
- University of North Carolina at Chapel Hill United States
- Center for Alcohol Studies Thailand
- Center for Alcohol Studies Thailand
- UNC Lineberger Comprehensive Cancer Center United States
- UNC Lineberger Comprehensive Cancer Center United States
Male, Patch-Clamp Techniques, Potassium Channels, Ethanol, Central Nervous System Depressants, Prefrontal Cortex, Real-Time Polymerase Chain Reaction, Rats, Rats, Sprague-Dawley, Alcoholism, Disease Models, Animal, Sex Factors, Interneurons, Cortical Excitability, Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels, Animals, Female, Single-Cell Analysis
Male, Patch-Clamp Techniques, Potassium Channels, Ethanol, Central Nervous System Depressants, Prefrontal Cortex, Real-Time Polymerase Chain Reaction, Rats, Rats, Sprague-Dawley, Alcoholism, Disease Models, Animal, Sex Factors, Interneurons, Cortical Excitability, Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels, Animals, Female, Single-Cell Analysis
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).39 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
