Regulation of Theta and Gamma Oscillations in Cortical Microcircuits

皮质微电路中 Theta 和 Gamma 振荡的调节

• 批准号: 8118819
• 负责人: Raquel E Gur
• 金额: $ 12.6万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8118819
• 关键词: Affect; Animals; Brain; Cells; Cerebral cortex; Cognition; Cognitive; Computer Simulation; Data; Detection; Disease; Equilibrium; Event-Related Potentials; Failure; Frequencies; Functional disorder; Gap Junctions; Generations; Goals; Human; Individual; Interneurons; Ketamine; Lead; Literature; Memory; Mental Depression; Modeling; N-Methylaspartate; Pathology; Patients; Perception; Phenytoin; Play; Process; Pyramidal Cells; Regulation; Reporting; Role; Schizophrenia; Signal Transduction; Sodium Channel; Stimulus; Symptoms; Synapses; base; cell type; deviant; insight; novel; simulation

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.

精神分裂症患者在事件相关电位（ERP）和伽马和伽马波中表现出异常， theta频率成分的变化。在伽马和θ振荡中出现明显的异常 由新奇的或异常的（不可预测的）刺激引起的。该项目的目标是调查，使用详细的 计算机模拟，这些伽马，θ和ERP异常如何可能来自细胞和突触 皮质病理学最近的研究揭示了伽马和θ 在皮层中产生振荡？伽玛和西塔都来自同一个皮层微回路 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发挥着不同的作用 γ与θ根据文献中的数据以及子项目0007、0008和0009的发现，我们将开发一个 详细的生物物理水平模拟这个微电路，我们将研究电路机制， 是theta和gamma产生的基础，特别是树突状间隙连接的作用。我们 假设在细胞类型特异性连接中，突触易化和抑制改变了平衡 因此，短期可塑性的异常可能是过度的伽马和 在精神分裂症患者中出现的θ波降低。我们提出了一个特定的电路模型， 对新奇刺激和熟悉刺激的反应该回路涉及皮质层III之间的已知连接， 和V.谷氨酸能功能障碍，如精神分裂症中所报道的，将导致这种新奇性的预测失败。 检测机制，并在伽马振荡和失配负相关的异常， ERP。我们专注于了解氯胺酮的NMDA拮抗剂作用， 伽马/θ异常类似于精神分裂症中的异常，并且已知其会诱导分离 症状我们假设苯妥英钠阻断持久性钠通道， 氯胺酮诱导的γ和θ异常，也可能在动物和人类模型中。 感知、认知和记忆与大脑中特定的电子信号有关？ 细胞在低（θ）和高（γ）频率下放电的振荡。我们将研究这些 振荡是由大脑皮层中的特定回路产生的，突触的异常是如何产生的？ 据报道，精神分裂症患者大脑中的信号传导引起了这些改变的振荡。这种理解可能 导致深入了解精神分裂症如何影响认知过程，以及细胞机制 导致了疾病的症状