Effects of Biological Noise Sources on Neuronal Dynamics

描述（改编自申请人的摘要）：单个神经细胞通常 不可靠：重复呈现相同的刺激可以产生 不同的动作电位序列因为这种反应 变异性限制了神经系统编码的准确性， 生物物理学的基础是非常重要的。这件事的直接目标是 该项目旨在了解神经元噪声的两个主要来源-突触 从突触前细胞接收的信号中的噪声和由突触前细胞引起的信道噪声 离子通道的概率门控-有助于并与 海马结构兴奋性神经元的动力学， 与学习和记忆有关内侧内嗅神经兴奋性神经元 皮层（MEC）和肉为这些实验提供了一个强大的试验平台 有几个原因例如：这些神经元中的一些表现出突出的 可能限制响应可靠性并影响网络响应的信道噪声; 不同种类的神经元有着截然不同的节奏特性， 这意味着在噪声条件下对比刺激偏好;这些 神经元在健康和受损的人类记忆中起着至关重要的作用。 个脑袋 将使用标准方法进行电生理学实验， 新开发的随机动态箝位技术。后一种方法允许 直接探索特定生物噪声源的因果作用， 塑造神经元电动力学和可靠性。四个假设将是 测试： a. MEC和海马中的兴奋性神经元表现出显著水平的 信道噪声 B。可靠性的属性显着不同的主细胞之间的 海马结构 C.通道和突触噪声影响电动力学和可靠性， mec所 D.生物噪声对仿生网络行为的影响 模拟 该项目的长期目标是-提高我们对如何 分子水平的事件有助于兴奋性、节律性和编码 神经细胞的特性-对改善人类健康很重要。一 对这种联系的机械理解可能会导致新的诊断， 治疗几种使人衰弱的神经系统疾病， 海马区的信息处理能力，包括 颞叶癫痫和中风相关的细胞死亡。

DESCRIPTION(adapted from applicant's abstract): Single nerve cells are often unreliable: repeated presentations of identical stimuli can generate significantly different trains of action potentials. Because this response variability limits the accuracy of encoding by the nervous system, its biophysical underpinnings are of great interest. The immediate goal of this project is to understand how two major sources of neuronal noise - synaptic noise in the signal received from presynaptic cells and channel noise caused by the probabilistic gating of ion channels - contribute to and interact with the dynamics of excitatory neurons of the hippocampal formation, a brain region implicated in learning and memory. Excitatory neurons of the medial entorhinal cortex (MEC) and hippocarnpus provide a powerful test-bed for these experiments for several reasons. For example: some of these neurons exhibit prominent channel noise that may limit response reliability and shape network responses; different classes of these neurons have contrasting rhythmic properties that imply contrasting stimulus preferences under noisy conditions; and these neurons play a critical role in human memory in the healthy and compromised brain. Electrophysiological experiments will be conducted using standard methods and newly developed stochastic dynamic clamp technology. The latter approach allows direct exploration of the causal roles of specific biological noise sources in shaping neuronal electrical dynamics and reliability. Four hypotheses will be tested: A. Excitatory neurons in MEC and hippocampus exhibit significant levels of channel noise B. Properties of reliability differ significantly among principal cells of the hippocampal formation C. Channel and synaptic noise influence electrical dynamics and reliability in the MEC D. Biological noise influences the behavior of biologically-inspired network simulations The long-term goal of this project - to enhance our understanding of how molecular-level events contribute to excitability, rhythmicity, and encoding properties in nerve cells - is important for improving human health. A mechanistic understanding of this connection may lead to novel diagnoses and treatments for several debilitating neurological disorders that disrupt the information-processing capabilities of the hippocampal region, including temporal-lobe epilepsy and stroke-related cell death.