Deletion of AMPA receptor GluA1 subunit gene (Gria1) causes circadian rhythm disruption and aberrant responses to environmental cues.
Deletion of AMPA receptor GluA1 subunit gene (Gria1) causes circadian rhythm disruption and aberrant responses to environmental cues.
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AMPA受体GluA1亚基基因（Gria1）的缺失会导致昼夜节律紊乱以及对环境线索的异常反应。
DOI：
10.1038/s41398-021-01690-3
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发表时间：
2021-11-15
影响因子：
6.8
通讯作者：
Peirson SN
中科院分区：
文献类型：
--
作者：
Ang G;Brown LA;Tam SKE;Davies KE;Foster RG;Harrison PJ;Sprengel R;Vyazovskiy VV;Oliver PL;Bannerman DM;Peirson SN
谷氨酸α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体GluA 1亚基功能障碍和突触可塑性缺陷与精神分裂症、睡眠和昼夜节律破坏有关。为了研究GluA 1在昼夜节律和睡眠行为中的作用，我们使用车轮运行，被动红外和基于视频的家庭笼活动监测来评估GluA 1敲除小鼠（Gria 1 −/−）的日常休息-活动曲线。我们发现，这些小鼠表现出各种昼夜节律异常，包括失调，碎片化和更多变的休息-活动模式。此外，他们表现出增强的，但短暂的，对光→暗和暗→光转换的行为觉醒，以及减弱的日光诱导的活动抑制（负掩蔽）。在下丘脑视交叉上核（SCN）中，强光诱导的cFos信号（前1-2 h神经元活动的分子标志物）减弱，表明SCN中的光敏感性降低。然而，在核心（腹内侧）与壳（背外侧）SCN亚区中差异表达的两种神经肽-血管活性肠肽（VIP）和精氨酸加压素（AVP）的表达水平的神经解剖学分布没有变化，已知这两种神经肽对SCN内的神经元同步和昼夜节律性都很重要。在运动皮层（M1/M2区），在夜间cFos水平的个体间变异性增加，反映了夜间光照下运动活动的个体间变异性增加。最后，在自发气味识别任务中，GluA 1敲除者的短期记忆由于对最近遇到的熟悉气味的注意力增强而受损。这些异常是由于AMPA受体介导的信号改变类似，并可能有助于睡眠和昼夜节律中断和注意力缺陷在精神分裂症的不同形式。
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.
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影响因子：
6.6
作者：
Barch, DM;Carter, CS;Cohen, JD
通讯作者：
Cohen, JD
影响因子：
--
作者：
Chuluun, Bayarsaikhan;Pittaras, Elsa;Heller, H. Craig
通讯作者：
Heller, H. Craig
影响因子：
2
作者：
Cui, Wen;Darby-King, Andrea;Harley, Carolyn W.
通讯作者：
Harley, Carolyn W.
DOI：
10.1016/0169-328x(94)00247-c
发表时间：
1995-04-01
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
EASTWOOD, SL;MCDONALD, B;HARRISON, PJ
通讯作者：
HARRISON, PJ
影响因子：
4.2
作者：
Biello, Stephany M.;Bonsall, David R.;Lall, Gurprit S.
通讯作者：
Lall, Gurprit S.