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Dopamine D(3) Receptors Inhibit Hippocampal Gamma Oscillations by Disturbing CA3 Pyramidal Cell Firing Synchrony

Cortical gamma oscillations are associated with cognitive processes and are altered in several neuropsychiatric conditions such as schizophrenia and Alzheimer’s disease. Since dopamine D(3) receptors are possible targets in treatment of these conditions, it is of great importance to understand their...

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Autores principales: Lemercier, Clément E., Schulz, Steffen B., Heidmann, Karin E., Kovács, Richard, Gerevich, Zoltan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4702013/
https://www.ncbi.nlm.nih.gov/pubmed/26779018
http://dx.doi.org/10.3389/fphar.2015.00297
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author Lemercier, Clément E.
Schulz, Steffen B.
Heidmann, Karin E.
Kovács, Richard
Gerevich, Zoltan
author_facet Lemercier, Clément E.
Schulz, Steffen B.
Heidmann, Karin E.
Kovács, Richard
Gerevich, Zoltan
author_sort Lemercier, Clément E.
collection PubMed
description Cortical gamma oscillations are associated with cognitive processes and are altered in several neuropsychiatric conditions such as schizophrenia and Alzheimer’s disease. Since dopamine D(3) receptors are possible targets in treatment of these conditions, it is of great importance to understand their role in modulation of gamma oscillations. The effect of D(3) receptors on gamma oscillations and the underlying cellular mechanisms were investigated by extracellular local field potential and simultaneous intracellular sharp micro-electrode recordings in the CA3 region of the hippocampus in vitro. D(3) receptors decreased the power and broadened the bandwidth of gamma oscillations induced by acetylcholine or kainate. Blockade of the D(3) receptors resulted in faster synchronization of the oscillations, suggesting that endogenous dopamine in the hippocampus slows down the dynamics of gamma oscillations by activation of D(3) receptors. Investigating the underlying cellular mechanisms for these effects showed that D(3) receptor activation decreased the rate of action potentials (APs) during gamma oscillations and reduced the precision of the AP phase coupling to the gamma cycle in CA3 pyramidal cells. The results may offer an explanation how selective activation of D(3) receptors may impair cognition and how, in converse, D(3) antagonists may exert pro-cognitive and antipsychotic effects.
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spelling pubmed-47020132016-01-15 Dopamine D(3) Receptors Inhibit Hippocampal Gamma Oscillations by Disturbing CA3 Pyramidal Cell Firing Synchrony Lemercier, Clément E. Schulz, Steffen B. Heidmann, Karin E. Kovács, Richard Gerevich, Zoltan Front Pharmacol Pharmacology Cortical gamma oscillations are associated with cognitive processes and are altered in several neuropsychiatric conditions such as schizophrenia and Alzheimer’s disease. Since dopamine D(3) receptors are possible targets in treatment of these conditions, it is of great importance to understand their role in modulation of gamma oscillations. The effect of D(3) receptors on gamma oscillations and the underlying cellular mechanisms were investigated by extracellular local field potential and simultaneous intracellular sharp micro-electrode recordings in the CA3 region of the hippocampus in vitro. D(3) receptors decreased the power and broadened the bandwidth of gamma oscillations induced by acetylcholine or kainate. Blockade of the D(3) receptors resulted in faster synchronization of the oscillations, suggesting that endogenous dopamine in the hippocampus slows down the dynamics of gamma oscillations by activation of D(3) receptors. Investigating the underlying cellular mechanisms for these effects showed that D(3) receptor activation decreased the rate of action potentials (APs) during gamma oscillations and reduced the precision of the AP phase coupling to the gamma cycle in CA3 pyramidal cells. The results may offer an explanation how selective activation of D(3) receptors may impair cognition and how, in converse, D(3) antagonists may exert pro-cognitive and antipsychotic effects. Frontiers Media S.A. 2016-01-06 /pmc/articles/PMC4702013/ /pubmed/26779018 http://dx.doi.org/10.3389/fphar.2015.00297 Text en Copyright © 2016 Lemercier, Schulz, Heidmann, Kovács and Gerevich. 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) or licensor 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
Lemercier, Clément E.
Schulz, Steffen B.
Heidmann, Karin E.
Kovács, Richard
Gerevich, Zoltan
Dopamine D(3) Receptors Inhibit Hippocampal Gamma Oscillations by Disturbing CA3 Pyramidal Cell Firing Synchrony
title Dopamine D(3) Receptors Inhibit Hippocampal Gamma Oscillations by Disturbing CA3 Pyramidal Cell Firing Synchrony
title_full Dopamine D(3) Receptors Inhibit Hippocampal Gamma Oscillations by Disturbing CA3 Pyramidal Cell Firing Synchrony
title_fullStr Dopamine D(3) Receptors Inhibit Hippocampal Gamma Oscillations by Disturbing CA3 Pyramidal Cell Firing Synchrony
title_full_unstemmed Dopamine D(3) Receptors Inhibit Hippocampal Gamma Oscillations by Disturbing CA3 Pyramidal Cell Firing Synchrony
title_short Dopamine D(3) Receptors Inhibit Hippocampal Gamma Oscillations by Disturbing CA3 Pyramidal Cell Firing Synchrony
title_sort dopamine d(3) receptors inhibit hippocampal gamma oscillations by disturbing ca3 pyramidal cell firing synchrony
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4702013/
https://www.ncbi.nlm.nih.gov/pubmed/26779018
http://dx.doi.org/10.3389/fphar.2015.00297
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