Properties of Axons and Synaptic Communication in the Neocortex

新皮质中轴突和突触通讯的特性

基本信息

批准号：
7760193
负责人：
David McCormick
金额：
$ 35.84万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-02-15 至 2012-01-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Traditionally, communication between neurons in the cerebral cortex, and, indeed, within much of the brain, is believed to be mediated largely or solely through the rate and pattern of action potentials in a pulse or digital code. Recently, however, we have shown that the average amplitude of synaptic potentials evoked by action potentials is dependent upon the membrane potential of the presynaptic neuron and that these membrane potential changes travel long distances down the axon. This means that information communication between nearby cortical neurons may use a combined pulse and graded or analog and digital code. Here we will examine the mechanisms of this possible analog code. Specifically, we will examine the mechanisms by which the membrane potential of cortical neurons can influence the amplitude of synaptic potentials that the neuron induces in nearby cells. We will perform whole cell recordings from synaptically connected pairs of neurons in prefrontal cortical slices maintained in vitro. In addition, we will examine the possible involvement of changes in presynaptic Calcium concentrations through two-photon imaging of Ca2+ levels in presynaptic boutons while their parent soma is moved to different membrane potentials. Our investigations will also examine the electrophysiological properties of intracortical axons, particularly those properties that may be involved in detecting changes in membrane potential at the soma. We are particularly interested in the properties of voltage-dependent K+ currents within intracortical axons and how these may control axonal excitability. To examine these in detail, we will perform simultaneous whole cell patch clamp recordings from the soma and axon of cortical neurons during the application of voltage clamp steps and examine the respond of the axons to the application of toxins that are specific for different types of K+ channel. Be performing whole cell recordings from intracortical axons in mice in which particular K+ channels have been knocked out, we will be able to examine the involvement of specific ionic channels and subunits in these effects. Through this combination of synaptic and axonal electrophysiological investigations, we will achieve a more detailed and integrated understanding of how information communication operates within the cerebral cortex. This information will allow us to better manage disorders of axonal and synaptic communication including multiple sclerosis and epilepsy. PUBLIC HEALTH RELEVANCE: The proper function of synaptic transmission and axons, the output of neurons, is critical to the proper functioning of the brain, particularly the cerebral cortex. Numerous neurological disorders result from disruption of synaptic and axonal function. Our study will examine important basic properties of synaptic and axonal function in the cerebral cortex.

描述（由申请人提供）：传统上，脑皮质中的神经元之间的交流，实际上，在大脑的大部分地区，被认为是通过脉冲或数字代码中的动作电位的速率和模式来介导的。然而，最近，我们已经表明，动作电位引起的突触电位的平均振幅取决于突触前神经元的膜电位，并且这些膜电位变化沿轴突沿轴突延伸很长。这意味着附近皮质神经元之间的信息通信可能会使用组合的脉冲，分级或模拟和数字代码。在这里，我们将检查此可能的模拟代码的机制。具体而言，我们将研究皮质神经元的膜电位可以影响神经元在附近细胞中诱导的突触电位的幅度的机制。我们将在体外维持的前额叶皮质切片中的突触连接的神经元对进行全细胞记录。此外，我们将通过将其父soma转移到不同的膜电位的同时，通过在突触前胸子中的Ca2+水平的两光子成像来检查突触前钙浓度的变化。我们的研究还将检查皮质内轴突的电生理特性，尤其是那些可能参与SOMA膜电位变化的特性。我们对心脏内轴突中电压依赖性K+电流的性质特别感兴趣，以及它们如何控制轴突兴奋性。为了详细检查这些这些，我们将在应用电压夹步骤的过程中同时执行来自皮质神经元的SOMA和轴突的全细胞贴片夹记录，并检查轴突对适用于不同类型的K+通道的毒素的响应。从已将特定的K+通道的小鼠中的皮质内轴突进行全细胞记录中，我们将能够检查特定离子通道和亚基参与这些作用。通过突触和轴突电生理研究的组合，我们将对信息通信在大脑皮质中的运作方式进行更详细和综合的理解。这些信息将使我们能够更好地管理轴突和突触通信的疾病，包括多发性硬化和癫痫。公共卫生相关性：突触传递和轴突的正确功能，即神经元的输出，对于大脑的正常功能，尤其是大脑皮层至关重要。突触和轴突功能的破坏导致了许多神经系统疾病。我们的研究将检查大脑皮质中突触和轴突功能的重要基本特性。