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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2021-11-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-021-01690-3 |
| _version_ | 1818822993938219008 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-18T23:32:55Z |
| format | Article |
| id | doaj.art-db96924aa90f4475ae84a2e870b1ccac |
| institution | Directory Open Access Journal |
| issn | 2158-3188 |
| language | English |
| last_indexed | 2024-12-18T23:32:55Z |
| publishDate | 2021-11-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj.art-db96924aa90f4475ae84a2e870b1ccac2022-12-21T20:47:38ZengNature Publishing GroupTranslational Psychiatry2158-31882021-11-0111111710.1038/s41398-021-01690-3Deletion of AMPA receptor GluA1 subunit gene (Gria1) causes circadian rhythm disruption and aberrant responses to environmental cuesGauri Ang0Laurence A. Brown1Shu K. E. Tam2Kay E. Davies3Russell G. Foster4Paul J. Harrison5Rolf Sprengel6Vladyslav V. Vyazovskiy7Peter L. Oliver8David M. Bannerman9Stuart N. Peirson10Department of Physiology, Anatomy and Genetics, University of OxfordSleep and Circadian Neuroscience Institute (SCNi), Nuffield Department of Clinical Neurosciences, University of OxfordSleep and Circadian Neuroscience Institute (SCNi), Nuffield Department of Clinical Neurosciences, University of OxfordDepartment of Physiology, Anatomy and Genetics, University of OxfordSleep and Circadian Neuroscience Institute (SCNi), Nuffield Department of Clinical Neurosciences, University of OxfordDepartment of Psychiatry, University of Oxford, Warneford HospitalResearch Group of the Max Planck Institute for Medical Research at the Institute for Anatomy and Cell Biology, Heidelberg UniversityDepartment of Physiology, Anatomy and Genetics, University of OxfordDepartment of Physiology, Anatomy and Genetics, University of OxfordDepartment of Experimental Psychology, University of OxfordSleep and Circadian Neuroscience Institute (SCNi), Nuffield Department of Clinical Neurosciences, University of OxfordAbstract 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.https://doi.org/10.1038/s41398-021-01690-3 |
| spellingShingle | 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 Translational Psychiatry |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41398-021-01690-3 |
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