Conventional measures of intrinsic excitability are poor estimators of neuronal activity under realistic synaptic inputs.

Activity-dependent regulation of intrinsic excitability has been shown to greatly contribute to the overall plasticity of neuronal circuits. Such neuroadaptations are commonly investigated in patch clamp experiments using current step stimulation and the resulting input-output functions are analyzed...

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Autores principales:	Adrienn Szabó, Katalin Schlett, Attila Szücs
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/8294bbfd9d1b49289a85dcff545ce297
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spelling	oai:doaj.org-article:8294bbfd9d1b49289a85dcff545ce2972021-12-02T19:57:46ZConventional measures of intrinsic excitability are poor estimators of neuronal activity under realistic synaptic inputs.1553-734X1553-735810.1371/journal.pcbi.1009378https://doaj.org/article/8294bbfd9d1b49289a85dcff545ce2972021-09-01T00:00:00Zhttps://doi.org/10.1371/journal.pcbi.1009378https://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Activity-dependent regulation of intrinsic excitability has been shown to greatly contribute to the overall plasticity of neuronal circuits. Such neuroadaptations are commonly investigated in patch clamp experiments using current step stimulation and the resulting input-output functions are analyzed to quantify alterations in intrinsic excitability. However, it is rarely addressed, how such changes translate to the function of neurons when they operate under natural synaptic inputs. Still, it is reasonable to expect that a strong correlation and near proportional relationship exist between static firing responses and those evoked by synaptic drive. We challenge this view by performing a high-yield electrophysiological analysis of cultured mouse hippocampal neurons using both standard protocols and simulated synaptic inputs via dynamic clamp. We find that under these conditions the neurons exhibit vastly different firing responses with surprisingly weak correlation between static and dynamic firing intensities. These contrasting responses are regulated by two intrinsic K-currents mediated by Kv1 and Kir channels, respectively. Pharmacological manipulation of the K-currents produces differential regulation of the firing output of neurons. Static firing responses are greatly increased in stuttering type neurons under blocking their Kv1 channels, while the synaptic responses of the same neurons are less affected. Pharmacological blocking of Kir-channels in delayed firing type neurons, on the other hand, exhibit the opposite effects. Our subsequent computational model simulations confirm the findings in the electrophysiological experiments and also show that adaptive changes in the kinetic properties of such currents can even produce paradoxical regulation of the firing output.Adrienn SzabóKatalin SchlettAttila SzücsPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 17, Iss 9, p e1009378 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Adrienn Szabó Katalin Schlett Attila Szücs Conventional measures of intrinsic excitability are poor estimators of neuronal activity under realistic synaptic inputs.
description	Activity-dependent regulation of intrinsic excitability has been shown to greatly contribute to the overall plasticity of neuronal circuits. Such neuroadaptations are commonly investigated in patch clamp experiments using current step stimulation and the resulting input-output functions are analyzed to quantify alterations in intrinsic excitability. However, it is rarely addressed, how such changes translate to the function of neurons when they operate under natural synaptic inputs. Still, it is reasonable to expect that a strong correlation and near proportional relationship exist between static firing responses and those evoked by synaptic drive. We challenge this view by performing a high-yield electrophysiological analysis of cultured mouse hippocampal neurons using both standard protocols and simulated synaptic inputs via dynamic clamp. We find that under these conditions the neurons exhibit vastly different firing responses with surprisingly weak correlation between static and dynamic firing intensities. These contrasting responses are regulated by two intrinsic K-currents mediated by Kv1 and Kir channels, respectively. Pharmacological manipulation of the K-currents produces differential regulation of the firing output of neurons. Static firing responses are greatly increased in stuttering type neurons under blocking their Kv1 channels, while the synaptic responses of the same neurons are less affected. Pharmacological blocking of Kir-channels in delayed firing type neurons, on the other hand, exhibit the opposite effects. Our subsequent computational model simulations confirm the findings in the electrophysiological experiments and also show that adaptive changes in the kinetic properties of such currents can even produce paradoxical regulation of the firing output.
format	article
author	Adrienn Szabó Katalin Schlett Attila Szücs
author_facet	Adrienn Szabó Katalin Schlett Attila Szücs
author_sort	Adrienn Szabó
title	Conventional measures of intrinsic excitability are poor estimators of neuronal activity under realistic synaptic inputs.
title_short	Conventional measures of intrinsic excitability are poor estimators of neuronal activity under realistic synaptic inputs.
title_full	Conventional measures of intrinsic excitability are poor estimators of neuronal activity under realistic synaptic inputs.
title_fullStr	Conventional measures of intrinsic excitability are poor estimators of neuronal activity under realistic synaptic inputs.
title_full_unstemmed	Conventional measures of intrinsic excitability are poor estimators of neuronal activity under realistic synaptic inputs.
title_sort	conventional measures of intrinsic excitability are poor estimators of neuronal activity under realistic synaptic inputs.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/8294bbfd9d1b49289a85dcff545ce297
work_keys_str_mv	AT adriennszabo conventionalmeasuresofintrinsicexcitabilityarepoorestimatorsofneuronalactivityunderrealisticsynapticinputs AT katalinschlett conventionalmeasuresofintrinsicexcitabilityarepoorestimatorsofneuronalactivityunderrealisticsynapticinputs AT attilaszucs conventionalmeasuresofintrinsicexcitabilityarepoorestimatorsofneuronalactivityunderrealisticsynapticinputs
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Conventional measures of intrinsic excitability are poor estimators of neuronal activity under realistic synaptic inputs.

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