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Elevating Endogenous GABA Levels with GAT-1 Blockade Modulates Evoked but Not Induced Responses in Human Visual Cortex

The electroencephalographic/magnetoencephalographic (EEG/MEG) signal is generated primarily by the summation of the postsynaptic currents of cortical principal cells. At a microcircuit level, these glutamatergic principal cells are reciprocally connected to GABAergic interneurons. Here we investigat...

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Autores principales: Muthukumaraswamy, Suresh D, Myers, Jim F M, Wilson, Sue J, Nutt, David J, Hamandi, Khalid, Lingford-Hughes, Anne, Singh, Krish D
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3629410/
https://www.ncbi.nlm.nih.gov/pubmed/23361120
http://dx.doi.org/10.1038/npp.2013.9
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author Muthukumaraswamy, Suresh D
Myers, Jim F M
Wilson, Sue J
Nutt, David J
Hamandi, Khalid
Lingford-Hughes, Anne
Singh, Krish D
author_facet Muthukumaraswamy, Suresh D
Myers, Jim F M
Wilson, Sue J
Nutt, David J
Hamandi, Khalid
Lingford-Hughes, Anne
Singh, Krish D
author_sort Muthukumaraswamy, Suresh D
collection PubMed
description The electroencephalographic/magnetoencephalographic (EEG/MEG) signal is generated primarily by the summation of the postsynaptic currents of cortical principal cells. At a microcircuit level, these glutamatergic principal cells are reciprocally connected to GABAergic interneurons. Here we investigated the relative sensitivity of visual evoked and induced responses to altered levels of endogenous GABAergic inhibition. To do this, we pharmacologically manipulated the GABA system using tiagabine, which blocks the synaptic GABA transporter 1, and so increases endogenous GABA levels. In a single-blinded and placebo-controlled crossover study of 15 healthy participants, we administered either 15 mg of tiagabine or a placebo. We recorded whole-head MEG, while participants viewed a visual grating stimulus, before, 1, 3 and 5 h post tiagabine ingestion. Using beamformer source localization, we reconstructed responses from early visual cortices. Our results showed no change in either stimulus-induced gamma-band amplitude increases or stimulus-induced alpha amplitude decreases. However, the same data showed a 45% reduction in the evoked response component at ∼80 ms. These data demonstrate that, in early visual cortex the evoked response shows a greater sensitivity compared with induced oscillations to pharmacologically increased endogenous GABA levels. We suggest that previous studies correlating GABA concentrations as measured by magnetic resonance spectroscopy to gamma oscillation frequency may reflect underlying variations such as interneuron/inhibitory synapse density rather than functional synaptic GABA concentrations.
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spelling pubmed-36294102013-05-01 Elevating Endogenous GABA Levels with GAT-1 Blockade Modulates Evoked but Not Induced Responses in Human Visual Cortex Muthukumaraswamy, Suresh D Myers, Jim F M Wilson, Sue J Nutt, David J Hamandi, Khalid Lingford-Hughes, Anne Singh, Krish D Neuropsychopharmacology Original Article The electroencephalographic/magnetoencephalographic (EEG/MEG) signal is generated primarily by the summation of the postsynaptic currents of cortical principal cells. At a microcircuit level, these glutamatergic principal cells are reciprocally connected to GABAergic interneurons. Here we investigated the relative sensitivity of visual evoked and induced responses to altered levels of endogenous GABAergic inhibition. To do this, we pharmacologically manipulated the GABA system using tiagabine, which blocks the synaptic GABA transporter 1, and so increases endogenous GABA levels. In a single-blinded and placebo-controlled crossover study of 15 healthy participants, we administered either 15 mg of tiagabine or a placebo. We recorded whole-head MEG, while participants viewed a visual grating stimulus, before, 1, 3 and 5 h post tiagabine ingestion. Using beamformer source localization, we reconstructed responses from early visual cortices. Our results showed no change in either stimulus-induced gamma-band amplitude increases or stimulus-induced alpha amplitude decreases. However, the same data showed a 45% reduction in the evoked response component at ∼80 ms. These data demonstrate that, in early visual cortex the evoked response shows a greater sensitivity compared with induced oscillations to pharmacologically increased endogenous GABA levels. We suggest that previous studies correlating GABA concentrations as measured by magnetic resonance spectroscopy to gamma oscillation frequency may reflect underlying variations such as interneuron/inhibitory synapse density rather than functional synaptic GABA concentrations. Nature Publishing Group 2013-05 2013-01-30 /pmc/articles/PMC3629410/ /pubmed/23361120 http://dx.doi.org/10.1038/npp.2013.9 Text en Copyright © 2013 American College of Neuropsychopharmacology http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
spellingShingle Original Article
Muthukumaraswamy, Suresh D
Myers, Jim F M
Wilson, Sue J
Nutt, David J
Hamandi, Khalid
Lingford-Hughes, Anne
Singh, Krish D
Elevating Endogenous GABA Levels with GAT-1 Blockade Modulates Evoked but Not Induced Responses in Human Visual Cortex
title Elevating Endogenous GABA Levels with GAT-1 Blockade Modulates Evoked but Not Induced Responses in Human Visual Cortex
title_full Elevating Endogenous GABA Levels with GAT-1 Blockade Modulates Evoked but Not Induced Responses in Human Visual Cortex
title_fullStr Elevating Endogenous GABA Levels with GAT-1 Blockade Modulates Evoked but Not Induced Responses in Human Visual Cortex
title_full_unstemmed Elevating Endogenous GABA Levels with GAT-1 Blockade Modulates Evoked but Not Induced Responses in Human Visual Cortex
title_short Elevating Endogenous GABA Levels with GAT-1 Blockade Modulates Evoked but Not Induced Responses in Human Visual Cortex
title_sort elevating endogenous gaba levels with gat-1 blockade modulates evoked but not induced responses in human visual cortex
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3629410/
https://www.ncbi.nlm.nih.gov/pubmed/23361120
http://dx.doi.org/10.1038/npp.2013.9
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