PHYSIOLOGICAL ROLES OF ION CHANNELS IN A SMALL NETWORK

描述：（改编自研究者的摘要） 简单的行为是由神经元网络产生的，它们以复杂的方式相互作用 和非线性方式。行为网络的输出由以下因素决定 网络内突触相互作用的模式和强度以及 不同网络神经元独特的内在放电特性。这些 突触和放电特性依次由不同的比率产生 每个神经元表达的离子通道和受体基因 网络。我们的目标是架起从基因表达到神经网络的桥梁 功能，显示单个基因如何有助于塑造行为输出 来自神经网络。为了实现这一目标，我们正在研究一组角色 14-神经元幽门网络内的钾和钙通道基因 龙虾口胃神经节。该网络是描述最清楚的网络之一 神经网络：所有突触连接都是已知的，并且发射 所有神经元的特性都很好理解。我们建议操纵 该网络中单个已识别神经元中离子通道的基因表达 更好地理解网络功能的规则。有3个具体目标 为了实现这个目标。首先，我们将完成正在进行的克隆项目 Shaker 家族的基因并分析其生物物理特性 电压依赖性 K 通道以及两个钙通道。其次，我们将 确定幽门网络中的哪些神经元表达这些基因，以及在哪里 在神经元中，蛋白质被靶向。三、增加表达 通过注射有义RNA，将这些基因转移到单个神经元中，或者减少 通过注射显性失活、反义或双链进行表达 RNA，并确定它如何改变 RNA 的放电和突触特性 神经元和幽门网络的活动模式。这种“分子 神经行为学”方法将使我们能够研究一个基因的影响 因此，网络的行为输出一次一个通道，这在 过去只能通过理论数学模型才能实现。

DESCRIPTION: (Adapted from the Investigator's Abstract) Simple behaviors are generated by networks of neurons, interacting in complex and nonlinear ways. The output from a behavioral network is determined by the pattern and strength of synaptic interactions within the network as well as the unique intrinsic firing properties of the different network neurons. These synaptic and firing properties are generated in turn by the differing ratios of ion channels and receptor genes that are expressed by each neuron in the network. Our goal is to bridge the span from gene expression to neural network function, to show how single genes contribute to shaping the behavioral output from a neural network. To accomplish this, we are studying the roles of a set of potassium and calcium channel genes within the 14-neuron pyloric network in the lobster stomatogastric ganglion. This network is one of the best-described neural networks: all of the synaptic connections are known and the firing properties of all the neurons are well understood. We propose to manipulate gene expression for ion channels in single identified neurons in this network to better understand the rules of network function. There are 3 specific aims to accomplish this goal. First, we will complete our ongoing project to clone the genes for and analyze the biophysical properties of the Shaker family of voltage dependent K+ channels as well as two calcium channels. Second, we will determine which neurons in the pyloric network express these genes, and where in the neuron the proteins are targeted. Third, we will increase the expression of these genes in single neurons, using injections of sense RNA, or decrease expression with injections of dominant negative, antisense or double-stranded RNA, and determine how this alters the firing and synaptic properties of the neuron and the pattern of activity in the pyloric network. This "molecular neuroethological" approach will allow us to study the effects of one gene and thus one channel at a time on the behavioral output of a network, which in the past has only been possible with theoretical mathematical models.