Altered avalanche dynamics in a developmental NMDAR hypofunction model of cognitive impairment.
Altered avalanche dynamics in a developmental NMDAR hypofunction model of cognitive impairment.
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DOI：
10.1038/s41398-017-0060-z
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发表时间：
2018-01-10
影响因子：
6.8
通讯作者：
Plenz D
中科院分区：
文献类型：
--
作者：
Seshadri S;Klaus A;Winkowski DE;Kanold PO;Plenz D
皮层网络紊乱的活动模式有助于精神分裂症的病理生理。在啮齿动物模型中，一些证据暗示了SZ中NMDA受体功能低下，并且在早期神经发育过程中阻断NMDA受体信号传导会产生与精神分裂症患者相似的认知缺陷。然而，这些认知障碍背后的网络动态变化在很大程度上仍有待研究，尤其是在细胞水平上。在这里，我们使用体内双光子钙成像来描述与认知功能障碍并行发生的病理动态，在发育性NMDA受体功能减退模型中。我们观察到时空活动传播的同动性和特异性变化增加，这可能与先前未确定的持续性破裂表型有因果关系。这种表型可以通过NMDA受体协同激动剂d -丝氨酸或GABAB受体激动剂巴氯芬的急性治疗来恢复，同样可以恢复工作记忆表现。它不能通过光遗传抑制快速尖峰中间神经元来复制。这些结果为神经网络水平异常介导NMDA受体功能低下引起的认知障碍提供了新的见解。
Disturbed activity patterns in cortical networks contribute to the pathophysiology of schizophrenia (SZ). Several lines of evidence implicate NMDA receptor hypofunction in SZ, and blocking NMDA receptor signaling during early neurodevelopment produces cognitive deficits in rodent models that resemble those seen in schizophrenic patients. However, the altered network dynamics underlying these cognitive impairments largely remain to be characterized, especially at the cellular level. Here, we use in vivo two-photon calcium imaging to describe pathological dynamics, occurring in parallel with cognitive dysfunction, in a developmental NMDA receptor hypofunction model. We observed increased synchrony and specific alterations in spatiotemporal activity propagation, which could be causally linked to a previously unidentified persistent bursting phenotype. This phenotype was rescued by acute treatment with the NMDA receptor co-agonist D-serine or the GABAB receptor agonist baclofen, which similarly rescued working memory performance. It was not reproduced by optogenetic inhibition of fast-spiking interneurons. These results provide novel insight into network-level abnormalities mediating the cognitive impairment induced by NMDA receptor hypofunction.
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DOI：
10.1103/physreve.79.061922
发表时间：
2009-06
期刊：
Physical review. E, Statistical, nonlinear, and soft matter physics
影响因子：
--
作者：
Fraiman D;Balenzuela P;Foss J;Chialvo DR
通讯作者：
Chialvo DR
影响因子：
2.5
作者：
AERTSEN, AMHJ;GERSTEIN, GL;PALM, G
通讯作者：
PALM, G
影响因子：
6.8
作者：
Gandal MJ;Sisti J;Klook K;Ortinski PI;Leitman V;Liang Y;Thieu T;Anderson R;Pierce RC;Jonak G;Gur RE;Carlson G;Siegel SJ
通讯作者：
Siegel SJ
影响因子：
7.6
作者：
Andersen, JD;Pouzet, B
通讯作者：
Pouzet, B
影响因子：
25
作者：
Greenberg, David S.;Houweling, Arthur R.;Kerr, Jason N. D.
通讯作者：
Kerr, Jason N. D.