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Unique Features of Network Bursts Emerge From the Complex Interplay of Excitatory and Inhibitory Receptors in Rat Neocortical Networks
Spontaneous network activity plays a fundamental role in the formation of functional networks during early development. The landmark of this activity is the recurrent emergence of intensive time-limited network bursts (NBs) rapidly spreading across the entire dissociated culture in vitro. The main e...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6742722/ https://www.ncbi.nlm.nih.gov/pubmed/31555093 http://dx.doi.org/10.3389/fncel.2019.00377 |
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author | Teppola, Heidi Aćimović, Jugoslava Linne, Marja-Leena |
author_facet | Teppola, Heidi Aćimović, Jugoslava Linne, Marja-Leena |
author_sort | Teppola, Heidi |
collection | PubMed |
description | Spontaneous network activity plays a fundamental role in the formation of functional networks during early development. The landmark of this activity is the recurrent emergence of intensive time-limited network bursts (NBs) rapidly spreading across the entire dissociated culture in vitro. The main excitatory mediators of NBs are glutamatergic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) and N-Methyl-D-aspartic-acid receptors (NMDARs) that express fast and slow ion channel kinetics, respectively. The fast inhibition of the activity is mediated through gamma-aminobutyric acid type A receptors (GABA(A)Rs). Although the AMPAR, NMDAR and GABA(A)R kinetics have been biophysically characterized in detail at the monosynaptic level in a variety of brain areas, the unique features of NBs emerging from the kinetics and the complex interplay of these receptors are not well understood. The goal of this study is to analyze the contribution of fast GABA(A)Rs on AMPAR- and NMDAR- mediated spontaneous NB activity in dissociated neonatal rat cortical cultures at 3 weeks in vitro. The networks were probed by both acute and gradual application of each excitatory receptor antagonist and combinations of acute excitatory and inhibitory receptor antagonists. At the same time, the extracellular network-wide activity was recorded with microelectrode arrays (MEAs). We analyzed the characteristic NB measures extracted from NB rate profiles and the distributions of interspike intervals, interburst intervals, and electrode recruitment time as well as the similarity of spatio-temporal patterns of network activity under different receptor antagonists. We show that NBs were rapidly initiated and recruited as well as diversely propagated by AMPARs and temporally and spatially maintained by NMDARs. GABA(A)Rs reduced the spiking frequency in AMPAR-mediated networks and dampened the termination of NBs in NMDAR-mediated networks as well as slowed down the recruitment of activity in all networks. Finally, we show characteristic super bursts composed of slow NBs with highly repetitive spatio-temporal patterns in gradually AMPAR blocked networks. To the best of our knowledge, this study is the first to unravel in detail how the three main mediators of synaptic transmission uniquely shape the NB characteristics, such as the initiation, maintenance, recruitment and termination of NBs in cortical cell cultures in vitro. |
format | Online Article Text |
id | pubmed-6742722 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-67427222019-09-25 Unique Features of Network Bursts Emerge From the Complex Interplay of Excitatory and Inhibitory Receptors in Rat Neocortical Networks Teppola, Heidi Aćimović, Jugoslava Linne, Marja-Leena Front Cell Neurosci Neuroscience Spontaneous network activity plays a fundamental role in the formation of functional networks during early development. The landmark of this activity is the recurrent emergence of intensive time-limited network bursts (NBs) rapidly spreading across the entire dissociated culture in vitro. The main excitatory mediators of NBs are glutamatergic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) and N-Methyl-D-aspartic-acid receptors (NMDARs) that express fast and slow ion channel kinetics, respectively. The fast inhibition of the activity is mediated through gamma-aminobutyric acid type A receptors (GABA(A)Rs). Although the AMPAR, NMDAR and GABA(A)R kinetics have been biophysically characterized in detail at the monosynaptic level in a variety of brain areas, the unique features of NBs emerging from the kinetics and the complex interplay of these receptors are not well understood. The goal of this study is to analyze the contribution of fast GABA(A)Rs on AMPAR- and NMDAR- mediated spontaneous NB activity in dissociated neonatal rat cortical cultures at 3 weeks in vitro. The networks were probed by both acute and gradual application of each excitatory receptor antagonist and combinations of acute excitatory and inhibitory receptor antagonists. At the same time, the extracellular network-wide activity was recorded with microelectrode arrays (MEAs). We analyzed the characteristic NB measures extracted from NB rate profiles and the distributions of interspike intervals, interburst intervals, and electrode recruitment time as well as the similarity of spatio-temporal patterns of network activity under different receptor antagonists. We show that NBs were rapidly initiated and recruited as well as diversely propagated by AMPARs and temporally and spatially maintained by NMDARs. GABA(A)Rs reduced the spiking frequency in AMPAR-mediated networks and dampened the termination of NBs in NMDAR-mediated networks as well as slowed down the recruitment of activity in all networks. Finally, we show characteristic super bursts composed of slow NBs with highly repetitive spatio-temporal patterns in gradually AMPAR blocked networks. To the best of our knowledge, this study is the first to unravel in detail how the three main mediators of synaptic transmission uniquely shape the NB characteristics, such as the initiation, maintenance, recruitment and termination of NBs in cortical cell cultures in vitro. Frontiers Media S.A. 2019-09-06 /pmc/articles/PMC6742722/ /pubmed/31555093 http://dx.doi.org/10.3389/fncel.2019.00377 Text en Copyright © 2019 Teppola, Aćimović and Linne. 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 | Neuroscience Teppola, Heidi Aćimović, Jugoslava Linne, Marja-Leena Unique Features of Network Bursts Emerge From the Complex Interplay of Excitatory and Inhibitory Receptors in Rat Neocortical Networks |
title | Unique Features of Network Bursts Emerge From the Complex Interplay of Excitatory and Inhibitory Receptors in Rat Neocortical Networks |
title_full | Unique Features of Network Bursts Emerge From the Complex Interplay of Excitatory and Inhibitory Receptors in Rat Neocortical Networks |
title_fullStr | Unique Features of Network Bursts Emerge From the Complex Interplay of Excitatory and Inhibitory Receptors in Rat Neocortical Networks |
title_full_unstemmed | Unique Features of Network Bursts Emerge From the Complex Interplay of Excitatory and Inhibitory Receptors in Rat Neocortical Networks |
title_short | Unique Features of Network Bursts Emerge From the Complex Interplay of Excitatory and Inhibitory Receptors in Rat Neocortical Networks |
title_sort | unique features of network bursts emerge from the complex interplay of excitatory and inhibitory receptors in rat neocortical networks |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6742722/ https://www.ncbi.nlm.nih.gov/pubmed/31555093 http://dx.doi.org/10.3389/fncel.2019.00377 |
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