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Ethanol-Sensitive Pacemaker Neurons in the Mouse External Globus Pallidus.

Karina P Abrahao1, Jessica H Chancey1, C Savio Chan2

  • 1Laboratory for Integrative Neuroscience, Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.

Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology
|November 10, 2016
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Summary

Ethanol selectively reduces firing in low-frequency pacemaker neurons in the external globus pallidus (GPe). This effect is mediated by large-conductance calcium-activated potassium (BK) channels, influencing basal ganglia circuitry.

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Area of Science:

  • Neuroscience
  • Neuropharmacology
  • Molecular Biology

Background:

  • Ethanol (alcohol) is widely used, yet its precise neuronal targets remain unclear.
  • Pacemaker neurons regulate brain circuits, but ethanol's impact on them is poorly understood.
  • External globus pallidus (GPe) pacemaker neurons are crucial for basal ganglia function, implicated in drug use.

Purpose of the Study:

  • To investigate the effects of ethanol on external globus pallidus (GPe) pacemaker neurons.
  • To identify specific neuronal subtypes within the GPe affected by ethanol.
  • To elucidate the molecular mechanisms underlying ethanol's action on GPe neurons.

Main Methods:

  • Patch-clamp electrophysiology was used to record firing rates of GPe neurons.
  • Specific mouse strains (Lhx6-EGFP, Npas1-tdTm) identified distinct neuronal subtypes.
  • In vivo electrophysiology and single-channel recordings assessed BK channel activity.

Main Results:

  • Ethanol dose-dependently decreased firing in low-frequency GPe neurons, sparing high-frequency ones.
  • Npas1-expressing neurons were particularly sensitive to lower ethanol concentrations.
  • Large-conductance voltage and Ca2+-activated K+ (BK) channel activity was essential for ethanol's effect, with ethanol increasing BK channel open probability.

Conclusions:

  • Ethanol exhibits selectivity in affecting pacemaker neuron subtypes within the GPe.
  • BK channels are key mediators of acute ethanol's effects on GPe neuronal firing.
  • Findings enhance understanding of how ethanol impacts basal ganglia circuitry.