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Mechanisms of variation in high frequency motor rhythms

高频运动节律的变化机制

基本信息

批准号：
7173335
负责人：
GERALD T SMITH
金额：
$ 21.09万
依托单位：
TRUSTEES OF INDIANA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-01-15 至 2008-12-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Almost all animals, including humans, produce rhythmic behavior. Studying the modulation and neural control of motor rhythms is important for several reasons. Such studies provide insight into the mechanisms by which organisms match motor outputs to their environment and also increase our understanding of disorders that disrupt the nervous system's ability to smoothly and spontaneously produce motor rhythms. Studies of central pattern generators (CPGs), networks of neurons that produce the timing signals for rhythmic behavior, have elucidated mechanisms of motor control at both systems and cellular levels. CPGs in vertebrate animals are often complex. Although in vitro preparations have allowed researchers to study mechanisms of pattern generation in vertebrate systems, identifying all of the component neurons and relating their intrinsic properties and connectivity to motor output is a challenging and active area of research. The proposed research will examine the cellular mechanisms of pattern generation in the electromotor system in weakly electric fish. This system controls the timing of electric organ discharges (EODs), which function in electrolocation and communication. The electromotor system is well suited for studying the neural mechanisms of motor rhythms for several reasons. First, the electromotor system contains only 3-4 different neuron types and is therefore a simpler neural circuit than most other vertebrate CPGs. Secondly, there is a straightforward relationship between the in vitro firing patterns of these neurons and the in vivo output of the circuit (the EOD), which allows us to relate observations at the cellular level to behavior. Finally, hormonally-induced sex differences and individual variation in EOD frequency are preserved in the firing patterns of neurons in reduced (in vitro) preparations. This feature will provide a rare opportunity to study the cellular mechanisms underlying sexual dimorphism and individual variation in rhythmic behavior. We will use intracellular current clamp recordings, pharmacological manipulations, and whole-cell voltage clamp to characterize ionic currents in electromotor neurons (EMNs), one of two spontaneously oscillating cell types in the electromotor circuit. These studies will allow us to generate a model that explains the spontaneous rhythmicity of EMNs. We will also examine the relationship between the biophysical properties of ionic currents in EMNs and individual variation in EOD frequency, which will allow us to examine how changes in neuronal excitability influence individual variation and sex differences in rhythmic behavior.

描述（由申请人提供）：几乎所有动物，包括人类，都会产生有节奏的行为。研究运动节律的调制和神经控制很重要，原因有几个。此类研究提供了对生物体将运动输出与其环境相匹配的机制的深入了解，并增加了我们对破坏神经系统平稳、自发地产生运动节律的能力的疾病的理解。对中枢模式发生器（CPG）（产生节律行为定时信号的神经元网络）的研究已经阐明了系统和细胞水平的运动控制机制。脊椎动物的 CPG 通常很复杂。尽管体外制剂使研究人员能够研究脊椎动物系统中模式生成的机制，但识别所有组成神经元并将其内在特性和与运动输出的连接性联系起来是一个具有挑战性和活跃的研究领域。拟议的研究将研究弱电鱼电动系统中模式生成的细胞机制。该系统控制电子器官放电（EOD）的时间，其在电定位和通信中发挥作用。出于多种原因，电动机系统非常适合研究运动节律的神经机制。首先，电动机系统仅包含 3-4 个不同的神经元类型，因此是比大多数其他脊椎动物 CPG 更简单的神经回路。其次，这些神经元的体外放电模式与体内电路输出（EOD）之间存在直接关系，这使我们能够将细胞水平的观察结果与行为联系起来。最后，激素引起的性别差异和 EOD 频率的个体差异保留在减少的（体外）制剂中神经元的放电模式中。这一特征将为研究性别二态性和节律行为的个体差异背后的细胞机制提供难得的机会。我们将使用细胞内电流钳记录、药理学操作和全细胞电压钳来表征电动神经元 (EMN) 中的离子电流，EMN 是电动电路中两种自发振荡细胞类型之一。这些研究将使我们能够生成一个模型来解释 EMN 的自发节律性。我们还将研究 EMN 中离子电流的生物物理特性与 EOD 频率的个体差异之间的关系，这将使我们能够研究神经元兴奋性的变化如何影响节律行为的个体差异和性别差异。