Modelling the spatial and temporal constrains of the GABAergic influence on neuronal excitability.

GABA (γ-amino butyric acid) is an inhibitory neurotransmitter in the adult brain that can mediate depolarizing responses during development or after neuropathological insults. Under which conditions GABAergic membrane depolarizations are sufficient to impose excitatory effects is hard to predict, as...

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Autores principales:	Aniello Lombardi, Heiko J Luhmann, Werner Kilb
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/761f0023803b4500a73e23a20867c0f8
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spelling	oai:doaj.org-article:761f0023803b4500a73e23a20867c0f82021-12-02T19:58:11ZModelling the spatial and temporal constrains of the GABAergic influence on neuronal excitability.1553-734X1553-735810.1371/journal.pcbi.1009199https://doaj.org/article/761f0023803b4500a73e23a20867c0f82021-11-01T00:00:00Zhttps://doi.org/10.1371/journal.pcbi.1009199https://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358GABA (γ-amino butyric acid) is an inhibitory neurotransmitter in the adult brain that can mediate depolarizing responses during development or after neuropathological insults. Under which conditions GABAergic membrane depolarizations are sufficient to impose excitatory effects is hard to predict, as shunting inhibition and GABAergic effects on spatiotemporal filtering of excitatory inputs must be considered. To evaluate at which reversal potential a net excitatory effect was imposed by GABA (EGABAThr), we performed a detailed in-silico study using simple neuronal topologies and distinct spatiotemporal relations between GABAergic and glutamatergic inputs. These simulations revealed for GABAergic synapses located at the soma an EGABAThr close to action potential threshold (EAPThr), while with increasing dendritic distance EGABAThr shifted to positive values. The impact of GABA on AMPA-mediated inputs revealed a complex temporal and spatial dependency. EGABAThr depends on the temporal relation between GABA and AMPA inputs, with a striking negative shift in EGABAThr for AMPA inputs appearing after the GABA input. The spatial dependency between GABA and AMPA inputs revealed a complex profile, with EGABAThr being shifted to values negative to EAPThr for AMPA synapses located proximally to the GABA input, while for distally located AMPA synapses the dendritic distance had only a minor effect on EGABAThr. For tonic GABAergic conductances EGABAThr was negative to EAPThr over a wide range of gGABAtonic values. In summary, these results demonstrate that for several physiologically relevant situations EGABAThr is negative to EAPThr, suggesting that depolarizing GABAergic responses can mediate excitatory effects even if EGABA did not reach EAPThr.Aniello LombardiHeiko J LuhmannWerner KilbPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 17, Iss 11, p e1009199 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Aniello Lombardi Heiko J Luhmann Werner Kilb Modelling the spatial and temporal constrains of the GABAergic influence on neuronal excitability.
description	GABA (γ-amino butyric acid) is an inhibitory neurotransmitter in the adult brain that can mediate depolarizing responses during development or after neuropathological insults. Under which conditions GABAergic membrane depolarizations are sufficient to impose excitatory effects is hard to predict, as shunting inhibition and GABAergic effects on spatiotemporal filtering of excitatory inputs must be considered. To evaluate at which reversal potential a net excitatory effect was imposed by GABA (EGABAThr), we performed a detailed in-silico study using simple neuronal topologies and distinct spatiotemporal relations between GABAergic and glutamatergic inputs. These simulations revealed for GABAergic synapses located at the soma an EGABAThr close to action potential threshold (EAPThr), while with increasing dendritic distance EGABAThr shifted to positive values. The impact of GABA on AMPA-mediated inputs revealed a complex temporal and spatial dependency. EGABAThr depends on the temporal relation between GABA and AMPA inputs, with a striking negative shift in EGABAThr for AMPA inputs appearing after the GABA input. The spatial dependency between GABA and AMPA inputs revealed a complex profile, with EGABAThr being shifted to values negative to EAPThr for AMPA synapses located proximally to the GABA input, while for distally located AMPA synapses the dendritic distance had only a minor effect on EGABAThr. For tonic GABAergic conductances EGABAThr was negative to EAPThr over a wide range of gGABAtonic values. In summary, these results demonstrate that for several physiologically relevant situations EGABAThr is negative to EAPThr, suggesting that depolarizing GABAergic responses can mediate excitatory effects even if EGABA did not reach EAPThr.
format	article
author	Aniello Lombardi Heiko J Luhmann Werner Kilb
author_facet	Aniello Lombardi Heiko J Luhmann Werner Kilb
author_sort	Aniello Lombardi
title	Modelling the spatial and temporal constrains of the GABAergic influence on neuronal excitability.
title_short	Modelling the spatial and temporal constrains of the GABAergic influence on neuronal excitability.
title_full	Modelling the spatial and temporal constrains of the GABAergic influence on neuronal excitability.
title_fullStr	Modelling the spatial and temporal constrains of the GABAergic influence on neuronal excitability.
title_full_unstemmed	Modelling the spatial and temporal constrains of the GABAergic influence on neuronal excitability.
title_sort	modelling the spatial and temporal constrains of the gabaergic influence on neuronal excitability.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/761f0023803b4500a73e23a20867c0f8
work_keys_str_mv	AT aniellolombardi modellingthespatialandtemporalconstrainsofthegabaergicinfluenceonneuronalexcitability AT heikojluhmann modellingthespatialandtemporalconstrainsofthegabaergicinfluenceonneuronalexcitability AT wernerkilb modellingthespatialandtemporalconstrainsofthegabaergicinfluenceonneuronalexcitability
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Modelling the spatial and temporal constrains of the GABAergic influence on neuronal excitability.

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