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Differential effects of group III metabotropic glutamate receptors on spontaneous inhibitory synaptic currents in spine-innervating double bouquet and parvalbumin-expressing dendrite-targeting GABAergic interneurons in human neocortex

Diverse neocortical GABAergic neurons specialize in synaptic targeting and their effects are modulated by presynaptic metabotropic glutamate receptors (mGluRs) suppressing neurotransmitter release in rodents, but their effects in human neocortex are unknown. We tested whether activation of group III...

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Autores principales: Lukacs, Istvan P, Francavilla, Ruggiero, Field, Martin, Hunter, Emily, Howarth, Michael, Horie, Sawa, Plaha, Puneet, Stacey, Richard, Livermore, Laurent, Ansorge, Olaf, Tamas, Gabor, Somogyi, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9977385/
https://www.ncbi.nlm.nih.gov/pubmed/35667019
http://dx.doi.org/10.1093/cercor/bhac195
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author Lukacs, Istvan P
Francavilla, Ruggiero
Field, Martin
Hunter, Emily
Howarth, Michael
Horie, Sawa
Plaha, Puneet
Stacey, Richard
Livermore, Laurent
Ansorge, Olaf
Tamas, Gabor
Somogyi, Peter
author_facet Lukacs, Istvan P
Francavilla, Ruggiero
Field, Martin
Hunter, Emily
Howarth, Michael
Horie, Sawa
Plaha, Puneet
Stacey, Richard
Livermore, Laurent
Ansorge, Olaf
Tamas, Gabor
Somogyi, Peter
author_sort Lukacs, Istvan P
collection PubMed
description Diverse neocortical GABAergic neurons specialize in synaptic targeting and their effects are modulated by presynaptic metabotropic glutamate receptors (mGluRs) suppressing neurotransmitter release in rodents, but their effects in human neocortex are unknown. We tested whether activation of group III mGluRs by L-AP4 changes GABA(A) receptor-mediated spontaneous inhibitory postsynaptic currents (sIPSCs) in 2 distinct dendritic spine-innervating GABAergic interneurons recorded in vitro in human neocortex. Calbindin-positive double bouquet cells (DBCs) had columnar “horsetail” axons descending through layers II–V innervating dendritic spines (48%) and shafts, but not somata of pyramidal and nonpyramidal neurons. Parvalbumin-expressing dendrite-targeting cell (PV-DTC) axons extended in all directions innervating dendritic spines (22%), shafts (65%), and somata (13%). As measured, 20% of GABAergic neuropil synapses innervate spines, hence DBCs, but not PV-DTCs, preferentially select spine targets. Group III mGluR activation paradoxically increased the frequency of sIPSCs in DBCs (to median 137% of baseline) but suppressed it in PV-DTCs (median 92%), leaving the amplitude unchanged. The facilitation of sIPSCs in DBCs may result from their unique GABAergic input being disinhibited via network effect. We conclude that dendritic spines receive specialized, diverse GABAergic inputs, and group III mGluRs differentially regulate GABAergic synaptic transmission to distinct GABAergic cell types in human cortex.
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spelling pubmed-99773852023-03-02 Differential effects of group III metabotropic glutamate receptors on spontaneous inhibitory synaptic currents in spine-innervating double bouquet and parvalbumin-expressing dendrite-targeting GABAergic interneurons in human neocortex Lukacs, Istvan P Francavilla, Ruggiero Field, Martin Hunter, Emily Howarth, Michael Horie, Sawa Plaha, Puneet Stacey, Richard Livermore, Laurent Ansorge, Olaf Tamas, Gabor Somogyi, Peter Cereb Cortex Original Article Diverse neocortical GABAergic neurons specialize in synaptic targeting and their effects are modulated by presynaptic metabotropic glutamate receptors (mGluRs) suppressing neurotransmitter release in rodents, but their effects in human neocortex are unknown. We tested whether activation of group III mGluRs by L-AP4 changes GABA(A) receptor-mediated spontaneous inhibitory postsynaptic currents (sIPSCs) in 2 distinct dendritic spine-innervating GABAergic interneurons recorded in vitro in human neocortex. Calbindin-positive double bouquet cells (DBCs) had columnar “horsetail” axons descending through layers II–V innervating dendritic spines (48%) and shafts, but not somata of pyramidal and nonpyramidal neurons. Parvalbumin-expressing dendrite-targeting cell (PV-DTC) axons extended in all directions innervating dendritic spines (22%), shafts (65%), and somata (13%). As measured, 20% of GABAergic neuropil synapses innervate spines, hence DBCs, but not PV-DTCs, preferentially select spine targets. Group III mGluR activation paradoxically increased the frequency of sIPSCs in DBCs (to median 137% of baseline) but suppressed it in PV-DTCs (median 92%), leaving the amplitude unchanged. The facilitation of sIPSCs in DBCs may result from their unique GABAergic input being disinhibited via network effect. We conclude that dendritic spines receive specialized, diverse GABAergic inputs, and group III mGluRs differentially regulate GABAergic synaptic transmission to distinct GABAergic cell types in human cortex. Oxford University Press 2022-06-07 /pmc/articles/PMC9977385/ /pubmed/35667019 http://dx.doi.org/10.1093/cercor/bhac195 Text en © The Author(s) 2022. Published by Oxford University Press. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Lukacs, Istvan P
Francavilla, Ruggiero
Field, Martin
Hunter, Emily
Howarth, Michael
Horie, Sawa
Plaha, Puneet
Stacey, Richard
Livermore, Laurent
Ansorge, Olaf
Tamas, Gabor
Somogyi, Peter
Differential effects of group III metabotropic glutamate receptors on spontaneous inhibitory synaptic currents in spine-innervating double bouquet and parvalbumin-expressing dendrite-targeting GABAergic interneurons in human neocortex
title Differential effects of group III metabotropic glutamate receptors on spontaneous inhibitory synaptic currents in spine-innervating double bouquet and parvalbumin-expressing dendrite-targeting GABAergic interneurons in human neocortex
title_full Differential effects of group III metabotropic glutamate receptors on spontaneous inhibitory synaptic currents in spine-innervating double bouquet and parvalbumin-expressing dendrite-targeting GABAergic interneurons in human neocortex
title_fullStr Differential effects of group III metabotropic glutamate receptors on spontaneous inhibitory synaptic currents in spine-innervating double bouquet and parvalbumin-expressing dendrite-targeting GABAergic interneurons in human neocortex
title_full_unstemmed Differential effects of group III metabotropic glutamate receptors on spontaneous inhibitory synaptic currents in spine-innervating double bouquet and parvalbumin-expressing dendrite-targeting GABAergic interneurons in human neocortex
title_short Differential effects of group III metabotropic glutamate receptors on spontaneous inhibitory synaptic currents in spine-innervating double bouquet and parvalbumin-expressing dendrite-targeting GABAergic interneurons in human neocortex
title_sort differential effects of group iii metabotropic glutamate receptors on spontaneous inhibitory synaptic currents in spine-innervating double bouquet and parvalbumin-expressing dendrite-targeting gabaergic interneurons in human neocortex
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9977385/
https://www.ncbi.nlm.nih.gov/pubmed/35667019
http://dx.doi.org/10.1093/cercor/bhac195
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