Mechanisms of variation in high frequency motor rhythms

描述(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。研究运动节律的调制和神经控制很重要，原因有几个。这类研究提供了对生物体将运动输出与环境相匹配的机制的洞察，也增加了我们对破坏神经系统顺畅和自发地产生运动节奏的能力的障碍的理解。对中枢模式发生器(CPGs)的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CPG通常是复杂的。尽管体外准备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固有属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。 这项拟议的研究将检验弱电鱼类电机系统中图案产生的细胞机制。该系统控制电子器官放电(EOD)的定时，电子器官放电具有电定位和通信功能。电动马达系统非常适合研究运动节律的神经机制，原因有几个。首先，电动系统只包含3-4种不同类型的神经元，因此与大多数其他脊椎动物CPG相比，它是一个更简单的神经电路。其次，在这些神经元的体外放电模式和电路(EOD)的体内输出之间存在直接的关系，这使得我们能够将细胞水平的观察与行为联系起来。最后，荷尔蒙诱导的性别差异和EOD频率的个体差异被保存在减少的(体外)准备中的神经元的放电模式中。这一特征将为研究性二型性和节律性行为个体差异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、药物操作和全细胞电压钳来表征电动马达神经元(EMN)的离子电流，EMN是电动马达电路中两种自发振荡细胞之一。这些研究将使我们能够产生一个模型来解释EMN的自发节律性。我们还将研究EMN中离子电流的生物物理性质与EOD频率的个体差异之间的关系，这将使我们能够检验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。

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.