Deletion of AMPA receptor GluA1 subunit gene (Gria1) causes circadian rhythm disruption and aberrant responses to environmental cues

Abstract Dysfunction of the glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor GluA1 subunit and deficits in synaptic plasticity are implicated in schizophrenia and sleep and circadian rhythm disruption. To investigate the role of GluA1 in circadian and sleep behaviour, w...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Gauri Ang, Laurence A. Brown, Shu K. E. Tam, Kay E. Davies, Russell G. Foster, Paul J. Harrison, Rolf Sprengel, Vladyslav V. Vyazovskiy, Peter L. Oliver, David M. Bannerman, Stuart N. Peirson
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/db96924aa90f4475ae84a2e870b1ccac
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:db96924aa90f4475ae84a2e870b1ccac
record_format	dspace
spelling	oai:doaj.org-article:db96924aa90f4475ae84a2e870b1ccac2021-11-21T12:07:49ZDeletion of AMPA receptor GluA1 subunit gene (Gria1) causes circadian rhythm disruption and aberrant responses to environmental cues10.1038/s41398-021-01690-32158-3188https://doaj.org/article/db96924aa90f4475ae84a2e870b1ccac2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41398-021-01690-3https://doaj.org/toc/2158-3188Abstract Dysfunction of the glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor GluA1 subunit and deficits in synaptic plasticity are implicated in schizophrenia and sleep and circadian rhythm disruption. To investigate the role of GluA1 in circadian and sleep behaviour, we used wheel-running, passive-infrared, and video-based home-cage activity monitoring to assess daily rest–activity profiles of GluA1-knockout mice (Gria1 −/−). We showed that these mice displayed various circadian abnormalities, including misaligned, fragmented, and more variable rest–activity patterns. In addition, they showed heightened, but transient, behavioural arousal to light→dark and dark→light transitions, as well as attenuated nocturnal-light-induced activity suppression (negative masking). In the hypothalamic suprachiasmatic nuclei (SCN), nocturnal-light-induced cFos signals (a molecular marker of neuronal activity in the preceding ~1–2 h) were attenuated, indicating reduced light sensitivity in the SCN. However, there was no change in the neuroanatomical distribution of expression levels of two neuropeptides―vasoactive intestinal peptide (VIP) and arginine vasopressin (AVP)―differentially expressed in the core (ventromedial) vs. shell (dorsolateral) SCN subregions and both are known to be important for neuronal synchronisation within the SCN and circadian rhythmicity. In the motor cortex (area M1/M2), there was increased inter-individual variability in cFos levels during the evening period, mirroring the increased inter-individual variability in locomotor activity under nocturnal light. Finally, in the spontaneous odour recognition task GluA1 knockouts’ short-term memory was impaired due to enhanced attention to the recently encountered familiar odour. These abnormalities due to altered AMPA-receptor-mediated signalling resemble and may contribute to sleep and circadian rhythm disruption and attentional deficits in different modalities in schizophrenia.Gauri AngLaurence A. BrownShu K. E. TamKay E. DaviesRussell G. FosterPaul J. HarrisonRolf SprengelVladyslav V. VyazovskiyPeter L. OliverDavid M. BannermanStuart N. PeirsonNature Publishing GrouparticleNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENTranslational Psychiatry, Vol 11, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Gauri Ang Laurence A. Brown Shu K. E. Tam Kay E. Davies Russell G. Foster Paul J. Harrison Rolf Sprengel Vladyslav V. Vyazovskiy Peter L. Oliver David M. Bannerman Stuart N. Peirson Deletion of AMPA receptor GluA1 subunit gene (Gria1) causes circadian rhythm disruption and aberrant responses to environmental cues
description	Abstract Dysfunction of the glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor GluA1 subunit and deficits in synaptic plasticity are implicated in schizophrenia and sleep and circadian rhythm disruption. To investigate the role of GluA1 in circadian and sleep behaviour, we used wheel-running, passive-infrared, and video-based home-cage activity monitoring to assess daily rest–activity profiles of GluA1-knockout mice (Gria1 −/−). We showed that these mice displayed various circadian abnormalities, including misaligned, fragmented, and more variable rest–activity patterns. In addition, they showed heightened, but transient, behavioural arousal to light→dark and dark→light transitions, as well as attenuated nocturnal-light-induced activity suppression (negative masking). In the hypothalamic suprachiasmatic nuclei (SCN), nocturnal-light-induced cFos signals (a molecular marker of neuronal activity in the preceding ~1–2 h) were attenuated, indicating reduced light sensitivity in the SCN. However, there was no change in the neuroanatomical distribution of expression levels of two neuropeptides―vasoactive intestinal peptide (VIP) and arginine vasopressin (AVP)―differentially expressed in the core (ventromedial) vs. shell (dorsolateral) SCN subregions and both are known to be important for neuronal synchronisation within the SCN and circadian rhythmicity. In the motor cortex (area M1/M2), there was increased inter-individual variability in cFos levels during the evening period, mirroring the increased inter-individual variability in locomotor activity under nocturnal light. Finally, in the spontaneous odour recognition task GluA1 knockouts’ short-term memory was impaired due to enhanced attention to the recently encountered familiar odour. These abnormalities due to altered AMPA-receptor-mediated signalling resemble and may contribute to sleep and circadian rhythm disruption and attentional deficits in different modalities in schizophrenia.
format	article
author	Gauri Ang Laurence A. Brown Shu K. E. Tam Kay E. Davies Russell G. Foster Paul J. Harrison Rolf Sprengel Vladyslav V. Vyazovskiy Peter L. Oliver David M. Bannerman Stuart N. Peirson
author_facet	Gauri Ang Laurence A. Brown Shu K. E. Tam Kay E. Davies Russell G. Foster Paul J. Harrison Rolf Sprengel Vladyslav V. Vyazovskiy Peter L. Oliver David M. Bannerman Stuart N. Peirson
author_sort	Gauri Ang
title	Deletion of AMPA receptor GluA1 subunit gene (Gria1) causes circadian rhythm disruption and aberrant responses to environmental cues
title_short	Deletion of AMPA receptor GluA1 subunit gene (Gria1) causes circadian rhythm disruption and aberrant responses to environmental cues
title_full	Deletion of AMPA receptor GluA1 subunit gene (Gria1) causes circadian rhythm disruption and aberrant responses to environmental cues
title_fullStr	Deletion of AMPA receptor GluA1 subunit gene (Gria1) causes circadian rhythm disruption and aberrant responses to environmental cues
title_full_unstemmed	Deletion of AMPA receptor GluA1 subunit gene (Gria1) causes circadian rhythm disruption and aberrant responses to environmental cues
title_sort	deletion of ampa receptor glua1 subunit gene (gria1) causes circadian rhythm disruption and aberrant responses to environmental cues
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/db96924aa90f4475ae84a2e870b1ccac
work_keys_str_mv	AT gauriang deletionofampareceptorglua1subunitgenegria1causescircadianrhythmdisruptionandaberrantresponsestoenvironmentalcues AT laurenceabrown deletionofampareceptorglua1subunitgenegria1causescircadianrhythmdisruptionandaberrantresponsestoenvironmentalcues AT shuketam deletionofampareceptorglua1subunitgenegria1causescircadianrhythmdisruptionandaberrantresponsestoenvironmentalcues AT kayedavies deletionofampareceptorglua1subunitgenegria1causescircadianrhythmdisruptionandaberrantresponsestoenvironmentalcues AT russellgfoster deletionofampareceptorglua1subunitgenegria1causescircadianrhythmdisruptionandaberrantresponsestoenvironmentalcues AT pauljharrison deletionofampareceptorglua1subunitgenegria1causescircadianrhythmdisruptionandaberrantresponsestoenvironmentalcues AT rolfsprengel deletionofampareceptorglua1subunitgenegria1causescircadianrhythmdisruptionandaberrantresponsestoenvironmentalcues AT vladyslavvvyazovskiy deletionofampareceptorglua1subunitgenegria1causescircadianrhythmdisruptionandaberrantresponsestoenvironmentalcues AT peterloliver deletionofampareceptorglua1subunitgenegria1causescircadianrhythmdisruptionandaberrantresponsestoenvironmentalcues AT davidmbannerman deletionofampareceptorglua1subunitgenegria1causescircadianrhythmdisruptionandaberrantresponsestoenvironmentalcues AT stuartnpeirson deletionofampareceptorglua1subunitgenegria1causescircadianrhythmdisruptionandaberrantresponsestoenvironmentalcues
_version_	1718419214468907008

Deletion of AMPA receptor GluA1 subunit gene (Gria1) causes circadian rhythm disruption and aberrant responses to environmental cues

Ejemplares similares