Optogenetic manipulation of an ascending arousal system tunes cortical broadband gamma power and reveals functional deficits relevant to schizophrenia.
Optogenetic manipulation of an ascending arousal system tunes cortical broadband gamma power and reveals functional deficits relevant to schizophrenia.
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上行唤醒系统的光遗传学操纵可调节皮质宽带伽马功率，并揭示与精神分裂症相关的功能缺陷。
DOI：
10.1038/s41380-020-0840-3
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发表时间：
2021-07
影响因子：
11
通讯作者：
Brown RE
中科院分区：
文献类型：
--
作者：
McNally JM;Aguilar DD;Katsuki F;Radzik LK;Schiffino FL;Uygun DS;McKenna JT;Strecker RE;Deisseroth K;Spencer KM;Brown RE
在精神分裂症患者和精神分裂症小鼠模型中观察到γ波段（30-80 Hz）范围内的宽带皮质脑电波（EEG）功率增加。它们也出现在人类和用拟精神病药物氯胺酮治疗的动物中。然而，可能导致宽带伽马功率增加的机制以及对认知和行为的病理生理学影响知之甚少。在这里，我们报告说，一个上升的觉醒系统的滋补光遗传学操纵双向调谐皮质宽带伽马功率，允许按需测试对皮质处理和行为的影响。含有钙结合蛋白小白蛋白（PV）的基底前脑（BF）神经元的恒定低瓦数光遗传学刺激增加了宽带γ频率功率，增加了运动活性，并损害了新物体识别。与此同时，任务相关的伽马波段振荡诱导列车的听觉刺激，或暴露于新的对象，受损，让人想起精神分裂症患者的研究结果。相反，BF-PV神经元的紧张性光遗传学抑制部分挽救了亚麻醉剂量的氯胺酮引起的宽带γ功率升高。这些结果支持这样的想法，即增加皮质宽带γ活动导致认知和行为障碍，并确定BF-PV活动作为这种活动的调节剂。因此，BF-PV神经元可能代表了一种新的药物治疗的目标，如精神分裂症，涉及异常增加皮层宽带γ活动。
Increases in broadband cortical electroencephalogram (EEG) power in the gamma band (30–80 Hz) range have been observed in schizophrenia patients and in mouse models of schizophrenia. They are also seen in humans and animals treated with the psychotomimetic agent ketamine. However, the mechanisms which can result in increased broadband gamma power and the pathophysiological implications for cognition and behavior are poorly understood. Here we report that tonic optogenetic manipulation of an ascending arousal system bi-directionally tunes cortical broadband gamma power, allowing on-demand tests of the effect on cortical processing and behavior. Constant, low wattage optogenetic stimulation of basal forebrain (BF) neurons containing the calcium-binding protein parvalbumin (PV) increased broadband gamma frequency power, increased locomotor activity, and impaired novel object recognition. Concomitantly, task-associated gamma band oscillations induced by trains of auditory stimuli, or exposure to novel objects, were impaired, reminiscent of findings in schizophrenia patients. Conversely, tonic optogenetic inhibition of BF-PV neurons partially rescued the elevated broadband gamma power elicited by subanesthetic doses of ketamine. These results support the idea that increased cortical broadband gamma activity leads to impairments in cognition and behavior and identify BF-PV activity as a modulator of this activity. As such, BF-PV neurons may represent a novel target for pharmacotherapy in disorders such as schizophrenia which involve aberrant increases in cortical broadband gamma activity.
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影响因子：
10.6
作者：
Foss-Feig JH;Adkinson BD;Ji JL;Yang G;Srihari VH;McPartland JC;Krystal JH;Murray JD;Anticevic A
通讯作者：
Anticevic A
影响因子：
16.2
作者：
Bastos AM;Usrey WM;Adams RA;Mangun GR;Fries P;Friston KJ
通讯作者：
Friston KJ
影响因子：
13.9
作者：
Buzsáki G;Wang XJ
通讯作者：
Wang XJ
影响因子：
16.6
作者：
Anaclet C;Pedersen NP;Ferrari LL;Venner A;Bass CE;Arrigoni E;Fuller PM
通讯作者：
Fuller PM
急性氯胺酮会使精神分裂症患者丘脑-皮层回路中与任务相关的伽马波段振荡失调。
DOI：
10.1093/brain/awy175
发表时间：
2018-08-01
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Grent-'t-Jong T;Rivolta D;Gross J;Gajwani R;Lawrie SM;Schwannauer M;Heidegger T;Wibral M;Singer W;Sauer A;Scheller B;Uhlhaas PJ
通讯作者：
Uhlhaas PJ