Motor pattern selection from a multifunctional motor circuit

描述(由申请人提供)：这项建议的长期目标是在细胞水平上确定不同的外在调制输入如何从构成行为基础的多功能神经网络中选择不同的运动模式。在所有动物中，神经调节使单个运动回路能够产生许多不同的活动模式，从而产生不同的行为。这种网络的多功能性很大程度上来自于调制递质的作用，它改变了神经元的细胞和突触属性。这些物质由感觉神经元、体液神经元和投射神经元释放，从而影响这些网络。到目前为止，关于特定的外在调节通路如何从多功能网络中选择特定的运动模式，人们知之甚少。这个问题将使用一个定义良好的模型系统来解决，即分离的蟹口胃神经系统，在该系统中，所有相关的神经元、突触和膜特性都可以被识别和操纵。具体地说，(1)将描述由新发现的外在调节通路触发的独特的咀嚼运动模式，并将其与先前研究的两种感觉通路所引发的模式进行比较。(2)这将包括确定调节这一作用的中间投射神经元，包括潜在的细胞和突触机制。这将有助于建立一个新的细胞水平模型，即不同的外部输入是否通过激活相同、重叠或不同组的投射神经元而从同一网络引发不同的运动输出。(3)不同的外部输入的重叠或顺序激活所产生的状态依赖和状态独立的后果也将被确定，以及(4)不同的共同释放的递质在这些过程中所扮演的角色。这项建议旨在结合细胞神经生理学、药理学和解剖学的方法来阐明从多功能网络中选择运动模式的一般原则。这将指导对更复杂、更难接近的哺乳动物神经系统的可比研究。由于所有动物的网络活动都有相同的组织原则，这项工作也将有助于更好地理解网络功能障碍，这些功能障碍会导致行为异常或丧失，例如脊髓损伤、中风或药物成瘾后调节状态的改变。

DESCRIPTION (provided by applicant): The long-term goal of this proposal is to determine, at the cellular level, how different extrinsic modulatory inputs select distinct motor patterns from multifunctional neural networks that underlie behavior. In all animals, neuromodulation enables single motor circuits to produce many different activity patterns, thereby producing distinct behaviors. The multifunctional character of such networks derives largely from the actions of modulatory transmitters which alter the cellular and synaptic properties of neurons. These substances are released by sensory, humoral and projection neurons to influence these networks. Thus far, little is known about how specific extrinsic modulatory pathways select a particular motor pattern from a multifunctional network. This issue will be addressed using a well-defined model system, the isolated crab stomatogastric nervous system, in which all of the relevant neurons, synapses and membrane properties can be identified and manipulated. Specifically, (1) the distinct chewing motor pattern triggered by a newly identified extrinsic modulatory pathway will be characterized and compared with the patterns elicited by two previously studied sensory pathways. (2) This will include identifying the intervening projection neurons that mediate this action, including the underlying cellular and synaptic mechanisms. This will help establish a new cellular-level model regarding whether distinct extrinsic inputs elicit different motor outputs from the same network by activating the same, overlapping or different sets of projection neurons. (3) The state-dependent and state- independent consequences from the overlapping or sequential activation of distinct extrinsic inputs will also be determined, as will (4) the roles played by distinct co-released transmitters in these processes. This proposal aims to combine cellular neurophysiological, pharmacological and anatomical approaches to elucidate general principles about motor pattern selection from multifunctional networks. This will guide comparable studies in the more complex and less accessible mammalian nervous system. Because the same organizing principles underlie network activity in all animals, this work will also facilitate a better understanding of network dysfunction that produces aberrant or loss of behavior, such as occurs as a consequence of spinal cord injury, stroke or altered modulatory states such as after drug addiction.