PHYSIOLOGICAL ROLES OF ION CHANNELS IN A SMALL NETWORK

描述：(改编自《调查者摘要》) 简单的行为是由神经元网络产生的，在复杂的环境中相互作用 和非线性的方式。行为网络的输出由 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 突触和放电特性由不同的比率依次产生 每个神经元表达的离子通道和受体基因 网络。我们的目标是搭建从基因表达到神经网络的桥梁 功能，以显示单个基因如何对塑造行为输出做出贡献 来自神经网络。为了做到这一点，我们正在研究一组角色 幽门14神经元网络中钾和钙通道基因的表达 龙虾的口胃神经节。这个网络是描述得最好的网络之一 神经网络：所有的突触连接都是已知的， 所有神经元的特性都很好地理解了。我们打算操纵 该网络中单个神经元离子通道的基因表达 以更好地了解网络运行的规律。有三个具体目标 来实现这一目标。首先，我们将完成我们正在进行的克隆项目 沙克病毒Shaker家族的基因及其生物物理特性分析 电压依赖性钾通道和两个钙通道。第二，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，蛋白质是靶向的。第三，我们将增加表达 通过注射正义RNA或减少这些基因在单个神经元中的表达 注射显性负链、反义或双链表达 RNA，并确定这如何改变神经元的激发和突触属性 神经元和幽门网络中的活动模式。这个“分子” 神经行为学“的方法将使我们能够研究一个基因和 因此，在网络的行为输出上一次一个频道，在 过去只有理论上的数学模型才有可能。

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.