Kv1.1 channels mediate network excitability and feed-forward inhibition in local amygdala circuits

Abstract Kv1.1 containing potassium channels play crucial roles towards dampening neuronal excitability. Mice lacking Kv1.1 subunits (Kcna1 −/− ) display recurrent spontaneous seizures and often exhibit sudden unexpected death. Seizures in Kcna1 −/− mice resemble those in well-characterized models o...

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Autores principales:	Samrat Thouta, Yiming Zhang, Esperanza Garcia, Terrance P. Snutch
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e9bfc6bc7c2a4821a0c1e8709e0da20f
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spelling	oai:doaj.org-article:e9bfc6bc7c2a4821a0c1e8709e0da20f2021-12-02T18:47:04ZKv1.1 channels mediate network excitability and feed-forward inhibition in local amygdala circuits10.1038/s41598-021-94633-32045-2322https://doaj.org/article/e9bfc6bc7c2a4821a0c1e8709e0da20f2021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94633-3https://doaj.org/toc/2045-2322Abstract Kv1.1 containing potassium channels play crucial roles towards dampening neuronal excitability. Mice lacking Kv1.1 subunits (Kcna1 −/− ) display recurrent spontaneous seizures and often exhibit sudden unexpected death. Seizures in Kcna1 −/− mice resemble those in well-characterized models of temporal lobe epilepsy known to involve limbic brain regions and spontaneous seizures result in enhanced cFos expression and neuronal death in the amygdala. Yet, the functional alterations leading to amygdala hyperexcitability have not been identified. In this study, we used Kcna1 −/− mice to examine the contributions of Kv1.1 subunits to excitability in neuronal subtypes from basolateral (BLA) and central lateral (CeL) amygdala known to exhibit distinct firing patterns. We also analyzed synaptic transmission properties in an amygdala local circuit predicted to be involved in epilepsy-related comorbidities. Our data implicate Kv1.1 subunits in controlling spontaneous excitatory synaptic activity in BLA pyramidal neurons. In the CeL, Kv1.1 loss enhances intrinsic excitability and impairs inhibitory synaptic transmission, notably resulting in dysfunction of feed-forward inhibition, a critical mechanism for controlling spike timing. Overall, we find inhibitory control of CeL interneurons is reduced in Kcna1 −/− mice suggesting that basal inhibitory network functioning is less able to prevent recurrent hyperexcitation related to seizures.Samrat ThoutaYiming ZhangEsperanza GarciaTerrance P. SnutchNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Samrat Thouta Yiming Zhang Esperanza Garcia Terrance P. Snutch Kv1.1 channels mediate network excitability and feed-forward inhibition in local amygdala circuits
description	Abstract Kv1.1 containing potassium channels play crucial roles towards dampening neuronal excitability. Mice lacking Kv1.1 subunits (Kcna1 −/− ) display recurrent spontaneous seizures and often exhibit sudden unexpected death. Seizures in Kcna1 −/− mice resemble those in well-characterized models of temporal lobe epilepsy known to involve limbic brain regions and spontaneous seizures result in enhanced cFos expression and neuronal death in the amygdala. Yet, the functional alterations leading to amygdala hyperexcitability have not been identified. In this study, we used Kcna1 −/− mice to examine the contributions of Kv1.1 subunits to excitability in neuronal subtypes from basolateral (BLA) and central lateral (CeL) amygdala known to exhibit distinct firing patterns. We also analyzed synaptic transmission properties in an amygdala local circuit predicted to be involved in epilepsy-related comorbidities. Our data implicate Kv1.1 subunits in controlling spontaneous excitatory synaptic activity in BLA pyramidal neurons. In the CeL, Kv1.1 loss enhances intrinsic excitability and impairs inhibitory synaptic transmission, notably resulting in dysfunction of feed-forward inhibition, a critical mechanism for controlling spike timing. Overall, we find inhibitory control of CeL interneurons is reduced in Kcna1 −/− mice suggesting that basal inhibitory network functioning is less able to prevent recurrent hyperexcitation related to seizures.
format	article
author	Samrat Thouta Yiming Zhang Esperanza Garcia Terrance P. Snutch
author_facet	Samrat Thouta Yiming Zhang Esperanza Garcia Terrance P. Snutch
author_sort	Samrat Thouta
title	Kv1.1 channels mediate network excitability and feed-forward inhibition in local amygdala circuits
title_short	Kv1.1 channels mediate network excitability and feed-forward inhibition in local amygdala circuits
title_full	Kv1.1 channels mediate network excitability and feed-forward inhibition in local amygdala circuits
title_fullStr	Kv1.1 channels mediate network excitability and feed-forward inhibition in local amygdala circuits
title_full_unstemmed	Kv1.1 channels mediate network excitability and feed-forward inhibition in local amygdala circuits
title_sort	kv1.1 channels mediate network excitability and feed-forward inhibition in local amygdala circuits
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e9bfc6bc7c2a4821a0c1e8709e0da20f
work_keys_str_mv	AT samratthouta kv11channelsmediatenetworkexcitabilityandfeedforwardinhibitioninlocalamygdalacircuits AT yimingzhang kv11channelsmediatenetworkexcitabilityandfeedforwardinhibitioninlocalamygdalacircuits AT esperanzagarcia kv11channelsmediatenetworkexcitabilityandfeedforwardinhibitioninlocalamygdalacircuits AT terrancepsnutch kv11channelsmediatenetworkexcitabilityandfeedforwardinhibitioninlocalamygdalacircuits
_version_	1718377713768595456

Kv1.1 channels mediate network excitability and feed-forward inhibition in local amygdala circuits

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