Mechanisms of variation in high frequency motor rhythms

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是重要的，原因有几个。这些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，也增加了我们对破坏神经系统平稳和自发产生运动节律的能力的疾病的理解。对中枢模式发生器（CPG）的研究已经从系统和细胞水平阐明了运动控制的机制，CPG是产生节律行为定时信号的神经元网络。脊椎动物中的CPG通常是复杂的。虽然体外制备允许研究人员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连接性与运动输出联系起来是一个具有挑战性和活跃的研究领域。 本研究将探讨弱电流鱼类的脑电系统中图案产生的细胞机制。该系统控制电器官放电（EOD）的定时，其在电定位和通信中起作用。由于以下几个原因，该系统非常适合于研究运动节律的神经机制。首先，CPG系统仅包含3-4种不同的神经元类型，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回路的体内输出（EOD）之间存在直接关系，这使我们能够将细胞水平的观察与行为联系起来。最后，在减少（在体外）制备的神经元的放电模式中保留了胚胎诱导的性别差异和EOD频率的个体差异。这一特点将提供一个难得的机会，研究细胞机制的性别二型性和个体差异的节奏行为。 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神经元（EMN）中的离子电流，EMN是神经元回路中两种自发振荡细胞类型之一。这些研究将使我们能够产生一个模型，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个体差异和节律行为的性别差异。

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.