Altered balance of excitatory and inhibitory learning in a genetically modified mouse model of glutamatergic dysfunction relevant to schizophrenia

Abstract The GluA1 AMPAR subunit (encoded by the Gria1 gene) has been implicated in schizophrenia. Gria1 knockout in mice results in recently experienced stimuli acquiring aberrantly high salience. This suggests that GluA1 may be important for learning that is sensitive to the temporal contiguity be...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	David J. Sanderson, Aletheia Lee, Rolf Sprengel, Peter H. Seeburg, Paul J. Harrison, David M. Bannerman
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b9ce5fc089bb499b97f2ec2b7df45736
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:b9ce5fc089bb499b97f2ec2b7df45736
record_format	dspace
spelling	oai:doaj.org-article:b9ce5fc089bb499b97f2ec2b7df457362021-12-02T12:31:46ZAltered balance of excitatory and inhibitory learning in a genetically modified mouse model of glutamatergic dysfunction relevant to schizophrenia10.1038/s41598-017-01925-82045-2322https://doaj.org/article/b9ce5fc089bb499b97f2ec2b7df457362017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01925-8https://doaj.org/toc/2045-2322Abstract The GluA1 AMPAR subunit (encoded by the Gria1 gene) has been implicated in schizophrenia. Gria1 knockout in mice results in recently experienced stimuli acquiring aberrantly high salience. This suggests that GluA1 may be important for learning that is sensitive to the temporal contiguity between events. To test this, mice were trained on a Pavlovian trace conditioning procedure in which the presentation of an auditory cue and food were separated by a temporal interval. Wild-type mice initially learnt, but with prolonged training came to withhold responding during the trace-conditioned cue, responding less than for another cue that was nonreinforced. Gria1 knockout mice, in contrast, showed sustained performance over training, responding more to the trace-conditioned cue than the nonreinforced cue. Therefore, the trace-conditioned cue acquired inhibitory properties (signalling the absence of food) in wild-type mice, but Gria1 deletion impaired the acquisition of inhibition, thus maintaining the stimulus as an excitatory predictor of food. Furthermore, when there was no trace both groups showed successful learning. These results suggest that cognitive abnormalities in disorders like schizophrenia in which gluatamatergic signalling is implicated may be caused by aberrant salience leading to a change in the nature of the information that is encoded.David J. SandersonAletheia LeeRolf SprengelPeter H. SeeburgPaul J. HarrisonDavid M. BannermanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q David J. Sanderson Aletheia Lee Rolf Sprengel Peter H. Seeburg Paul J. Harrison David M. Bannerman Altered balance of excitatory and inhibitory learning in a genetically modified mouse model of glutamatergic dysfunction relevant to schizophrenia
description	Abstract The GluA1 AMPAR subunit (encoded by the Gria1 gene) has been implicated in schizophrenia. Gria1 knockout in mice results in recently experienced stimuli acquiring aberrantly high salience. This suggests that GluA1 may be important for learning that is sensitive to the temporal contiguity between events. To test this, mice were trained on a Pavlovian trace conditioning procedure in which the presentation of an auditory cue and food were separated by a temporal interval. Wild-type mice initially learnt, but with prolonged training came to withhold responding during the trace-conditioned cue, responding less than for another cue that was nonreinforced. Gria1 knockout mice, in contrast, showed sustained performance over training, responding more to the trace-conditioned cue than the nonreinforced cue. Therefore, the trace-conditioned cue acquired inhibitory properties (signalling the absence of food) in wild-type mice, but Gria1 deletion impaired the acquisition of inhibition, thus maintaining the stimulus as an excitatory predictor of food. Furthermore, when there was no trace both groups showed successful learning. These results suggest that cognitive abnormalities in disorders like schizophrenia in which gluatamatergic signalling is implicated may be caused by aberrant salience leading to a change in the nature of the information that is encoded.
format	article
author	David J. Sanderson Aletheia Lee Rolf Sprengel Peter H. Seeburg Paul J. Harrison David M. Bannerman
author_facet	David J. Sanderson Aletheia Lee Rolf Sprengel Peter H. Seeburg Paul J. Harrison David M. Bannerman
author_sort	David J. Sanderson
title	Altered balance of excitatory and inhibitory learning in a genetically modified mouse model of glutamatergic dysfunction relevant to schizophrenia
title_short	Altered balance of excitatory and inhibitory learning in a genetically modified mouse model of glutamatergic dysfunction relevant to schizophrenia
title_full	Altered balance of excitatory and inhibitory learning in a genetically modified mouse model of glutamatergic dysfunction relevant to schizophrenia
title_fullStr	Altered balance of excitatory and inhibitory learning in a genetically modified mouse model of glutamatergic dysfunction relevant to schizophrenia
title_full_unstemmed	Altered balance of excitatory and inhibitory learning in a genetically modified mouse model of glutamatergic dysfunction relevant to schizophrenia
title_sort	altered balance of excitatory and inhibitory learning in a genetically modified mouse model of glutamatergic dysfunction relevant to schizophrenia
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/b9ce5fc089bb499b97f2ec2b7df45736
work_keys_str_mv	AT davidjsanderson alteredbalanceofexcitatoryandinhibitorylearninginageneticallymodifiedmousemodelofglutamatergicdysfunctionrelevanttoschizophrenia AT aletheialee alteredbalanceofexcitatoryandinhibitorylearninginageneticallymodifiedmousemodelofglutamatergicdysfunctionrelevanttoschizophrenia AT rolfsprengel alteredbalanceofexcitatoryandinhibitorylearninginageneticallymodifiedmousemodelofglutamatergicdysfunctionrelevanttoschizophrenia AT peterhseeburg alteredbalanceofexcitatoryandinhibitorylearninginageneticallymodifiedmousemodelofglutamatergicdysfunctionrelevanttoschizophrenia AT pauljharrison alteredbalanceofexcitatoryandinhibitorylearninginageneticallymodifiedmousemodelofglutamatergicdysfunctionrelevanttoschizophrenia AT davidmbannerman alteredbalanceofexcitatoryandinhibitorylearninginageneticallymodifiedmousemodelofglutamatergicdysfunctionrelevanttoschizophrenia
_version_	1718394301395763200

Altered balance of excitatory and inhibitory learning in a genetically modified mouse model of glutamatergic dysfunction relevant to schizophrenia

Ejemplares similares