Mechanisms of variation in high frequency motor rhythms

描述（由申请人提供）：几乎所有的动物，包括人类，都会产生有节奏的行为。研究运动节律的调节和神经控制是很重要的，原因有几个。这些研究提供了对有机体将运动输出与其环境相匹配的机制的深入了解，也增加了我们对破坏神经系统平稳自发产生运动节奏能力的疾病的理解。中枢模式发生器（central pattern generators, CPGs）是为节律性行为产生定时信号的神经元网络，其研究已经阐明了系统和细胞水平上的运动控制机制。脊椎动物的CPGs通常是复杂的。尽管体外制备使研究人员能够研究脊椎动物系统中模式产生的机制，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联系起来是一个具有挑战性和活跃的研究领域。

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.