Mechanisms Mediating Neural Network Modulation

描述：(申请人提供) 这项提议的长期目标是在细胞水平上决定如何 不同的感觉和下行输入会产生不同的运动模式 到构成行为基础的多功能神经网络。以前的工作在 许多模型系统表明，神经基础背后的一个共同原则 行为的特点是，单个神经网络产生许多不同的神经网络 活动模式，从而产生不同的行为。多功能的 这种网络的特征来自于调制的作用 改变细胞和突触特性的神经递质 网络神经元。到目前为止，关于神经系统如何 选择应由给定网络引发的活动模式。在这 将对上下文、已识别的投射和感觉神经元进行研究，以确定 这一遴选过程是如何安排的。这将包括一项决心 (A)神经递质的共同释放；(B) 依赖活性的递质释放调节，以及(C)激活 不同的投射神经元集合。这项提议旨在利用 定义良好的模型系统，螃蟹的口胃神经系统，以 阐明多递质调制神经元的细胞机制 从定义明确的网络中获得不同的输出。因为神经网络是 所有行为的基本构建块，以及许多相同的组织 关于所有动物的网络活动原理，这项工作旨在更好地 解释神经系统是如何产生行为的。这将促进 更好地了解会导致网络异常或丢失的网络功能障碍 行为，如脊髓损伤或中风后发生的行为。因为这件事 研究将对网络功能的调制进行研究，也将有所贡献 到必须理解以解决异常行为的一般原则 改变状态的在状态改变期间发生的，例如由于药物引起的 上瘾。这项提议旨在将细胞神经生理学、 用药理学和解剖学方法阐明 从多功能网络中选择电机模式。这将为我们提供指导 在更复杂的哺乳动物神经系统中进行的可比研究。

DESCRIPTION:(provided by applicant) The long-term goal of this proposal is to determine, at the cellular level, how distinct motor patterns are elicited by different sensory and descending inputs to multifunctional neural networks that underlie behavior. Previous work in many model systems showed that one common principle underlying the neural basis of behavior is that single neural networks produce many different neural activity patterns, thereby producing distinct behaviors. The multifunctional character of such networks derives from the actions of modulatory neurotransmitters which alter the cellular and synaptic properties of the network neurons. Thus far, little is known regarding how the nervous system selects which activity pattern should be elicited by a given network. In this context, identified projection and sensory neurons will be studied to determine how this selection process is orchestrated. This will include a determination of the roles played by the (a) co-release of neurotransmitters, (b) activity-dependent regulation of transmitter release, and (c) activation of distinct sets of projection neurons. This proposal aims to take advantage of a well-defined model system, the stomatogastric nervous system of the crab, to elucidate the cellular mechanisms whereby multitransmitter modulatory neurons elicit distinct outputs from well-defined networks. Because neural networks are basic building blocks underlying all behaviors, and many of the same organizing principles pertain to network activity in all animals, this work aims to better elucidate how the nervous system generates behavior. This will facilitate a better understanding of network dysfunction that produces aberrant or loss of behavior, such as occurs after spinal cord injury or stroke. Because this research will study the modulation of network function, it will also contribute to general principles that must be understood to address aberrant behaviors occurring during altered states, for example as occurs as a result of drug addiction. 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, mammalian nervous system.