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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2019.01402

Pharmacological antagonism of T-type calcium channels constrains rebound burst firing in two distinct subpopulations of GABA neurons in the rat ventral tegmental area: implications for α-lipoic acid

 Taylor Woodward1,  Vesna Tesic2, Vesna Jevtovic-Todorovic1, 3 and  Slobodan Todorovic4*
  • 1Department of Anesthesiology, School of Medicine, University of Colorado, United States
  • 2Department of Neurology, School of Medicine, University of Colorado, United States
  • 3Department of Anesthesiology, School of Medicine, University of Colorado, United States
  • 4University of Colorado Denver, United States

The ventral tegmental area (VTA) is a midbrain region highly involved in motivation and reward. A large body of work has investigated synaptic plasticity and ion channel excitability in this area, which has strong implication in drug abuse. We recently provided electrophysiological and pharmacological evidence that the CaV3.1 isoform of T-type voltage-gated calcium channels contributes to the excitability of VTA dopamine (DA) neurons. However, the role of T-channels in excitability of VTA gamma-amino-butyric acid (GABA) neurons remained unaddressed. Here, with a population study of rat VTA GABA neurons, we provide evidence that T-channels contribute to rebound spiking activity in two phenotypically distinct subpopulations of GABAergic neurons, each with differing electrophysiological characteristics. Additionally, we provide the first study to investigate the effect of α-lipoic acid (ALA) on ion channels in mesolimbic reward circuitry. Taken together, our population study and pharmacology experiments implicate T-channels as a target for therapies aimed at tempering VTA and mesolimbic circuit excitability.

Keywords: GABA, Low-voltage activated calcium channels, alpha lipoic acid, bursting, Ca2+, Ventral Tegemental Area (VTA), T-type calcium channel

Received: 22 Apr 2019; Accepted: 04 Nov 2019.

Copyright: © 2019 Woodward, Tesic, Jevtovic-Todorovic and Todorovic. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Mx. Slobodan Todorovic, University of Colorado Denver, Denver, United States, slobodan.todorovic@ucdenver.edu