Rhythms of the Nervous System

描述(申请人提供)：神经系统的节律与重要的行为和认知状态有关，包括注意力、工作记忆、联想记忆、自下而上的特征绑定、物体识别、感觉运动整合、知觉和语言处理。节律中的病理与精神分裂症和阿尔茨海默病有关。尽管这些节律在体外和体内都已被检测到，但它们如何参与认知仍不清楚。这一建议的总体目的是利用细胞和突触的生物物理信息进行建模研究，以了解神经系统中各种节律的起源和协调机制。这些信息中的一部分来自之前的实验。其他数据将在这里提出的实验中收集。该提案关注三个重要的节奏：伽马(30-80赫兹)、贝塔(12-30赫兹)和西塔(4-11赫兹)。这项工作的一个主要目标是了解产生节律的机制如何影响神经系统处理结构化输入的方式。有许多实验范例产生具有相同频率范围的不同版本的节奏。这些都是体内不同情况下的类似物，对药理扰动可能有不同的反应。在同一频率节律的不同版本中，有不同的突触电导是关键的，可能有不同类别的中间神经元参与。该模型旨在探索不同的固有电流和突触电流在个体节律产生中的作用以及它们之间的相互作用，包括嵌套节律和它们之间与行为状态变化相关的转换。同时进行的实验旨在揭示这类中间神经元的电生理和药理学特性，以及电突触在产生节律中的作用。还将有旨在梳理新大脑皮层不同层不同节奏的实验。其他实验范式将探索感觉刺激的影响，突触可塑性在节律之间转换中的重要性，以及伽马和西塔嵌套发生的条件。我们还将通过实验和建模来研究产生连贯伽马节奏的独立网络和分布在空间上的网络。

DESCRIPTION (provided by applicant): Rhythms of the nervous system have been linked to important behavioral and cognitive states, including attention, working memory, associative memory, bottom-up feature binding, object recognition, sensory motor integration, perception and language processing. Pathologies in the rhythms have been linked to schizophrenia and Alzheimer's disease. Although these rhythms have been detected both in vitro and in vivo, how they participate in cognition is still not understood. The general aim of this proposal is to make use of biophysical information about cells and synapses in modeling studies to understand the origin and mechanisms of coherence of the various rhythms displayed in nervous system. Some of this information exists from previous experiments. Other data will be gathered in experiments proposed here. The proposal focuses on three important rhythms: gamma (30-80 Hz), beta (12-30 Hz) and theta (4-11 Hz). A major goal of this work is to understand how the mechanisms that produce the rhythms influence the way the nervous system processes structured input. There are many experimental paradigms that produce different versions of rhythms with the same frequency range. These are analogues of different in vivo situations, and can have different reactions to pharmacological perturbations. In different versions of the same frequency rhythm, there are different synaptic conductances that are critical and there may be different classes of interneurons participating. The modeling aims to probe the roles of the different intrinsic and synaptic currents in producing the individual rhythms and the interactions among them, including nesting rhythms and the transitions among them that are associated with changes of behavioral state. Experiments, done in tandem, aim to reveal more details of the electrophysiological and pharmacological properties of the classes of interneurons, and roles of electrical synapses in producing rhythms. There will also be experiments aimed at teasing out different rhythms in different layers of the neocortex. Other experimental paradigms will probe effects of sensory stimuli, the importance of synaptic plasticity in the transformation among rhythms, and the conditions under which nesting of gamma and theta occur. We will also study, both experimentally and via modeling, separated networks that produce a coherent gamma rhythm, and networks distributed over space.