Cargando…

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

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 pharmacologic...

Descripción completa

Detalles Bibliográficos
Autores principales: Woodward, Taylor Joel, Tesic, Vesna, Stamenic, Tamara Timic, Jevtovic-Todorovic, Vesna, Todorovic, Slobodan M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889856/
https://www.ncbi.nlm.nih.gov/pubmed/31849661
http://dx.doi.org/10.3389/fphar.2019.01402
_version_ 1783475504340271104
author Woodward, Taylor Joel
Tesic, Vesna
Stamenic, Tamara Timic
Jevtovic-Todorovic, Vesna
Todorovic, Slobodan M.
author_facet Woodward, Taylor Joel
Tesic, Vesna
Stamenic, Tamara Timic
Jevtovic-Todorovic, Vesna
Todorovic, Slobodan M.
author_sort Woodward, Taylor Joel
collection PubMed
description 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 Ca(V)3.1 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.
format Online
Article
Text
id pubmed-6889856
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-68898562019-12-17 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 Woodward, Taylor Joel Tesic, Vesna Stamenic, Tamara Timic Jevtovic-Todorovic, Vesna Todorovic, Slobodan M. Front Pharmacol Pharmacology 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 Ca(V)3.1 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. Frontiers Media S.A. 2019-11-26 /pmc/articles/PMC6889856/ /pubmed/31849661 http://dx.doi.org/10.3389/fphar.2019.01402 Text en Copyright © 2019 Woodward, Tesic, Stamenic, Jevtovic-Todorovic and Todorovic http://creativecommons.org/licenses/by/4.0/ 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.
spellingShingle Pharmacology
Woodward, Taylor Joel
Tesic, Vesna
Stamenic, Tamara Timic
Jevtovic-Todorovic, Vesna
Todorovic, Slobodan M.
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889856/
https://www.ncbi.nlm.nih.gov/pubmed/31849661
http://dx.doi.org/10.3389/fphar.2019.01402
work_keys_str_mv AT woodwardtaylorjoel pharmacologicalantagonismofttypecalciumchannelsconstrainsreboundburstfiringintwodistinctsubpopulationsofgabaneuronsintheratventraltegmentalareaimplicationsforalipoicacid
AT tesicvesna pharmacologicalantagonismofttypecalciumchannelsconstrainsreboundburstfiringintwodistinctsubpopulationsofgabaneuronsintheratventraltegmentalareaimplicationsforalipoicacid
AT stamenictamaratimic pharmacologicalantagonismofttypecalciumchannelsconstrainsreboundburstfiringintwodistinctsubpopulationsofgabaneuronsintheratventraltegmentalareaimplicationsforalipoicacid
AT jevtovictodorovicvesna pharmacologicalantagonismofttypecalciumchannelsconstrainsreboundburstfiringintwodistinctsubpopulationsofgabaneuronsintheratventraltegmentalareaimplicationsforalipoicacid
AT todorovicslobodanm pharmacologicalantagonismofttypecalciumchannelsconstrainsreboundburstfiringintwodistinctsubpopulationsofgabaneuronsintheratventraltegmentalareaimplicationsforalipoicacid