Krystal John H, Anticevic Alan, Yang Genevieve J, Dragoi George, Driesen Naomi R, Wang Xiao-Jing, Murray John D
Department of PsychiatryYale University, New Haven; Department of Neurosciencex, Yale University School of Medicine, New Haven; Behavioral Health Services, Yale-New Haven Hospital, New Haven; Clinical Neurosciences Division, Veterans Affairs National Center for PTSD, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut.
Department of PsychiatryYale University, New Haven; Department of Psychology, Yale University, New Haven.
Biol Psychiatry. 2017 May 15;81(10):874-885. doi: 10.1016/j.biopsych.2017.01.004. Epub 2017 Jan 13.
The functional optimization of neural ensembles is central to human higher cognitive functions. When the functions through which neural activity is tuned fail to develop or break down, symptoms and cognitive impairments arise. This review considers ways in which disturbances in the balance of excitation and inhibition might develop and be expressed in cortical networks in association with schizophrenia. This presentation is framed within a developmental perspective that begins with disturbances in glutamate synaptic development in utero. It considers developmental correlates and consequences, including compensatory mechanisms that increase intrinsic excitability or reduce inhibitory tone. It also considers the possibility that these homeostatic increases in excitability have potential negative functional and structural consequences. These negative functional consequences of disinhibition may include reduced working memory-related cortical activity associated with the downslope of the "inverted-U" input-output curve, impaired spatial tuning of neural activity and impaired sparse coding of information, and deficits in the temporal tuning of neural activity and its implication for neural codes. The review concludes by considering the functional significance of noisy activity for neural network function. The presentation draws on computational neuroscience and pharmacologic and genetic studies in animals and humans, particularly those involving N-methyl-D-aspartate glutamate receptor antagonists, to illustrate principles of network regulation that give rise to features of neural dysfunction associated with schizophrenia. While this presentation focuses on schizophrenia, the general principles outlined in the review may have broad implications for considering disturbances in the regulation of neural ensembles in psychiatric disorders.
神经集群的功能优化对于人类的高级认知功能至关重要。当神经活动所依赖的功能未能正常发育或出现故障时，就会引发症状和认知障碍。本综述探讨了兴奋与抑制平衡失调在与精神分裂症相关的皮质网络中可能出现及表现的方式。这一阐述基于一种发育视角，始于子宫内谷氨酸突触发育的紊乱。它考量了发育方面的关联及后果，包括增加内在兴奋性或降低抑制性张力的代偿机制。它还探讨了这些兴奋性的稳态增加可能产生潜在负面功能和结构后果的可能性。去抑制的这些负面功能后果可能包括与“倒U形”输入 - 输出曲线下坡相关的工作记忆相关皮质活动减少、神经活动的空间调谐受损以及信息的稀疏编码受损，还有神经活动的时间调谐缺陷及其对神经编码的影响。综述最后考量了噪声活动对神经网络功能的功能意义。本阐述借鉴了动物和人类的计算神经科学以及药理和遗传学研究，特别是那些涉及N - 甲基 - D - 天冬氨酸谷氨酸受体拮抗剂的研究，以阐明导致与精神分裂症相关神经功能障碍特征的网络调节原则。虽然本阐述聚焦于精神分裂症，但综述中概述的一般原则可能对考虑精神疾病中神经集群调节的紊乱具有广泛意义。
