Selective reduction of AMPA currents onto hippocampal interneurons impairs network oscillatory activity.

Reduction of excitatory currents onto GABAergic interneurons in the forebrain results in impaired spatial working memory and altered oscillatory network patterns in the hippocampus. Whether this phenotype is caused by an alteration in hippocampal interneurons is not known because most studies employ...

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Autores principales:	Antonio Caputi, Elke C Fuchs, Kevin Allen, Corentin Le Magueresse, Hannah Monyer
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a2fa1ecb610f4b97b12869f46b842748
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spelling	oai:doaj.org-article:a2fa1ecb610f4b97b12869f46b8427482021-11-18T07:16:31ZSelective reduction of AMPA currents onto hippocampal interneurons impairs network oscillatory activity.1932-620310.1371/journal.pone.0037318https://doaj.org/article/a2fa1ecb610f4b97b12869f46b8427482012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22675480/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Reduction of excitatory currents onto GABAergic interneurons in the forebrain results in impaired spatial working memory and altered oscillatory network patterns in the hippocampus. Whether this phenotype is caused by an alteration in hippocampal interneurons is not known because most studies employed genetic manipulations affecting several brain regions. Here we performed viral injections in genetically modified mice to ablate the GluA4 subunit of the AMPA receptor in the hippocampus (GluA4(HC-/-) mice), thereby selectively reducing AMPA receptor-mediated currents onto a subgroup of hippocampal interneurons expressing GluA4. This regionally selective manipulation led to a strong spatial working memory deficit while leaving reference memory unaffected. Ripples (125-250 Hz) in the CA1 region of GluA4(HC-/-) mice had larger amplitude, slower frequency and reduced rate of occurrence. These changes were associated with an increased firing rate of pyramidal cells during ripples. The spatial selectivity of hippocampal pyramidal cells was comparable to that of controls in many respects when assessed during open field exploration and zigzag maze running. However, GluA4 ablation caused altered modulation of firing rate by theta oscillations in both interneurons and pyramidal cells. Moreover, the correlation between the theta firing phase of pyramidal cells and position was weaker in GluA4(HC-/-) mice. These results establish the involvement of AMPA receptor-mediated currents onto hippocampal interneurons for ripples and theta oscillations, and highlight potential cellular and network alterations that could account for the altered working memory performance.Antonio CaputiElke C FuchsKevin AllenCorentin Le MagueresseHannah MonyerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 6, p e37318 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Antonio Caputi Elke C Fuchs Kevin Allen Corentin Le Magueresse Hannah Monyer Selective reduction of AMPA currents onto hippocampal interneurons impairs network oscillatory activity.
description	Reduction of excitatory currents onto GABAergic interneurons in the forebrain results in impaired spatial working memory and altered oscillatory network patterns in the hippocampus. Whether this phenotype is caused by an alteration in hippocampal interneurons is not known because most studies employed genetic manipulations affecting several brain regions. Here we performed viral injections in genetically modified mice to ablate the GluA4 subunit of the AMPA receptor in the hippocampus (GluA4(HC-/-) mice), thereby selectively reducing AMPA receptor-mediated currents onto a subgroup of hippocampal interneurons expressing GluA4. This regionally selective manipulation led to a strong spatial working memory deficit while leaving reference memory unaffected. Ripples (125-250 Hz) in the CA1 region of GluA4(HC-/-) mice had larger amplitude, slower frequency and reduced rate of occurrence. These changes were associated with an increased firing rate of pyramidal cells during ripples. The spatial selectivity of hippocampal pyramidal cells was comparable to that of controls in many respects when assessed during open field exploration and zigzag maze running. However, GluA4 ablation caused altered modulation of firing rate by theta oscillations in both interneurons and pyramidal cells. Moreover, the correlation between the theta firing phase of pyramidal cells and position was weaker in GluA4(HC-/-) mice. These results establish the involvement of AMPA receptor-mediated currents onto hippocampal interneurons for ripples and theta oscillations, and highlight potential cellular and network alterations that could account for the altered working memory performance.
format	article
author	Antonio Caputi Elke C Fuchs Kevin Allen Corentin Le Magueresse Hannah Monyer
author_facet	Antonio Caputi Elke C Fuchs Kevin Allen Corentin Le Magueresse Hannah Monyer
author_sort	Antonio Caputi
title	Selective reduction of AMPA currents onto hippocampal interneurons impairs network oscillatory activity.
title_short	Selective reduction of AMPA currents onto hippocampal interneurons impairs network oscillatory activity.
title_full	Selective reduction of AMPA currents onto hippocampal interneurons impairs network oscillatory activity.
title_fullStr	Selective reduction of AMPA currents onto hippocampal interneurons impairs network oscillatory activity.
title_full_unstemmed	Selective reduction of AMPA currents onto hippocampal interneurons impairs network oscillatory activity.
title_sort	selective reduction of ampa currents onto hippocampal interneurons impairs network oscillatory activity.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/a2fa1ecb610f4b97b12869f46b842748
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Selective reduction of AMPA currents onto hippocampal interneurons impairs network oscillatory activity.

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