Regulation of Theta and Gamma Oscillations in Cortical Microcircuits

精神分裂症患者在事件相关电位(ERPs)和伽马和 这些事件相关电位的Theta频率分量。伽马和西塔振荡中出现明显的异常 由新奇的或者不寻常的(不可预知的)刺激引起的。这个项目的目标是调查，使用详细的 计算机模拟，这些伽马、西塔和事件相关电位异常是如何由细胞和突触引起的 大脑皮层病理学。最近的研究揭示了伽马和西塔的基本机制 震荡产生于大脑皮层？？伽马和西塔都来自同一个大脑皮层微回路。 涉及锥体细胞和两种类型的中间神经元。每种细胞类型在生成过程中扮演不同的角色 伽马VS西塔。基于文献中的数据和子项目0007、0008和0009的发现，我们将制定一个 详细的生物物理级模拟这种微电路，我们将检查电路机制 Theta和Gamma的强健生成是基础，特别是树突缝隙连接的作用。我们 假设突触易化和抑制在细胞类型特定的连接中改变平衡 因此，短期塑性的异常可能是过剩的伽马和 减少了精神分裂症患者的theta。我们提出了一个特定的电路模型来解释大脑皮质如何 对新的刺激和熟悉的刺激的反应？该回路涉及已知的皮质III层之间的连接 而V.谷氨酸能功能障碍，如在精神分裂症中所报道的，将导致这项新奇研究中预期的失败 探测机制，以及相关的伽马振荡异常和失配负性 企业资源计划。我们重点了解氯胺酮的NMDA拮抗作用，它产生 与精神分裂症类似的伽马/西塔异常，已知会导致分离 症状。我们假设，阻断持续性钠通道的苯妥英将逆转 氯胺酮引起的伽马和西塔异常，也可能在动物和人类模型中。 知觉、认知和记忆与大脑中特定的电信号有关？ 细胞在低(Theta)和高(Gamma)频率下的放电振荡。我们将调查这些问题是如何 振荡是由大脑皮层中的特定电路产生的，以及突触的异常 据报道，精神分裂症患者大脑中的信号会引起这些改变的振荡。这一理解可能 洞察精神分裂症如何影响认知过程，以及细胞机制 对这种疾病的症状负责。

Schizophrenic individuals show abnormalities in event related potentials (ERPs) and in the gamma and theta frequency components of these ERPs. Marked abnormalities occur in gamma and theta oscillations elicited by novel or deviant (unpredicted) stimuli. The goal of this project is to investigate, using detailed computer simulations, how these gamma, theta, and ERP abnormalities may arise from cellular and synaptic pathology in cortex. Recent studies have uncovered basic mechanisms by which gamma and theta oscillations are generated in cortex?both gamma and theta arise from the same cortical microcircuit involving pyramidal cells and two types of interneurons. Each cell type plays a different role in generating gamma vs. theta. Based on data from the literature, and findings from Subprojects 0007, 0008, and 0009, we will develop a detailed biophysical level simulation of this microcircuit, and we will examine the circuit mechanisms that underlie robust generation of theta and gamma, particularly the role of dendritic gap junctions. We hypothesize that synaptic facilitation and depression, in celltype specific connections, alters the balance between gamma and theta; thus, abnormalities in short-term plasticity may underlie the excess gamma and decreased theta seen in schizophrenic patients. We propose a specific circuit model for how the cortex responds to novel versus familiar stimuli?the circuit involves known connections between cortical layers III and V. Glutamtatergic dysfunction, as reported in schizophrenia, will lead to predicted failures in this novelty detection mechanism, and to associated abnormalities in gamma oscillations and the mismatch negativity in the ERP. We focus on understanding the NMDA antagonist actions of ketamine, which produces gamma/theta abnormalities similar to those in schizophrenia, and which is known to induce disassociative symptoms. We hypothesize that phenytoin, which blocks persistent sodium channels, will reverse the gamma and theta abnormalities induced by ketamine, and also possibly in animal and human models. Perception, cognition, and memory are associated with specific electrical signatures in the brain? oscillations of cell firing at low (theta) and high (gamma) frequencies. We will investigate how these oscillations are generated by specific circuits in the cerebral cortex, and how abnormalities in synaptic signaling reported in schizophrenic brains give rise to these altered oscillations. This understanding may lead to insight into how schizophrenia affects cognitive processes, and to the cellular mechanisms responsible for the symptoms of the disease.