MODULATION OF NEURONAL INPUT-OUTPUT BY IN VIVO-LIKE VOLTAGE FLUCTUATIONS

通过类体内电压波动调节神经元输入输出

• 批准号: 8682733
• 负责人: Fernando R. Fernandez
• 金额: $ 7.45万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-01 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8682733
• 关键词: Address; Affect; Animals; Area; Cells; Characteristics; Charge; Computer Simulation; Computer software; Data; Environment; Equilibrium; Event; Excitatory Synapse; Exhibits; Experimental Models; Frequencies; Generations; In Vitro; Inhibitory Synapse; Intracellular Membranes; Kinetics; Lead; Measures; Membrane; Modeling; Nature; Neurons; Neurosciences; Noise; Normal Statistical Distribution; Output; Phase; Physiological; Play; Preparation; Probability; Process; Property; Publishing; Pyramidal Cells; Records; Reporting; Rest; Role; Shapes; Slice; Stimulus; Synapses; Time; V1 neuron; Visual Cortex; Visual system structure; Work; awake; hippocampal pyramidal neuron; in vivo; in vivo Model; membrane model; nervous system disorder; novel; public health relevance; response; simulation; tool; visual process; visual processing; visual stimulus; voltage

DESCRIPTION (provided by applicant): A change in spike rate or timing is a fundamental output characteristic of neuronal response. Neuronal spike output, however, is characterized by a noisy or random nature such that the same environmental stimulus never generates the same precise count spike output. This is particular true for cortical neuronal spike discharge during states when the animal is awake or actively engaged with the environment. In part, the random nature of spike discharge is related to the underlying nature of membrane voltage fluctuations that are generated by seemingly random excitatory and inhibitory synaptic events. A large body of experimental and modeling work has focused on how membrane voltage fluctuations alter the input-output response of neurons. Often, noisy fluctuations in synaptic activity are thought of as "background" activity that modulates how neurons respond to deterministic set of inputs provided by only a few pre-synaptic neurons that are actively engaged in singling a stimulus. For example, background voltage fluctuations are thought to increase sensitivity to weak inputs in visual cortical neurons and hence provide a form of gain control or contrast invariance. As such, the nature of the background membrane voltage fluctuations plays a fundamental role in how neurons transform synaptic current inputs to spike output. In addressing these issues, previous modeling work has assumed that membrane voltage fluctuations can be described by normal (Gaussian) distributions with power spectra largely determined by the synaptic decay kinetics of excitatory and inhibitory synapses. Our preliminary analyses of in vivo membrane voltage fluctuations recorded in layer II V1 pyramidal cells, however, indicate that fluctuations have positively skewed distributions (i.e. non-Gaussian) and far less power at high frequencies than expected from filtering established through synaptic kinetics or membrane charge time. Given the central role of voltage fluctuations in cortical dynamics and computational models, it is crucial to understand both the nature of in vivo fluctuations and how our new observations concerning distributions and spectra of voltage affect input-output functions of cortical neurons. To address these issues, this project will analyze in vivo membrane voltage fluctuations and model their generation using a novel set of tool kits developed within our dynamic clamp software suite. We will then combine our simulations of synaptic activity with dynamic clamp to inject these forms of background activity to neurons in a slice preparation of layer II V1 cells an assess input-output functions.

描述（由申请人提供）：尖峰频率或时间的变化是神经元反应的基本输出特征。然而，神经元尖峰输出的特征在于噪声或随机性质，使得相同的环境刺激永远不会产生相同的精确计数尖峰输出。当动物处于清醒状态或积极参与环境时，皮层神经元的尖峰放电尤其如此。在某种程度上，尖峰放电的随机性与膜电压波动的基本性质有关，膜电压波动是由看似随机的兴奋性和抑制性突触事件产生的。大量的实验和建模工作集中在膜电压波动如何改变神经元的输入输出响应。通常，突触活动中的噪声波动被认为是“背景”活动，其调节神经元如何响应于由仅几个积极参与单一刺激的突触前神经元提供的确定性输入集。例如，背景电压波动被认为增加了视觉皮层神经元对弱输入的敏感性，因此提供了一种形式的增益控制或对比度不变性。因此，背景膜电压波动的性质在神经元如何将突触电流输入转换为尖峰输出中起着重要作用。在解决这些问题，以前的建模工作已经假设，膜电压波动可以描述为正常（高斯）分布，功率谱主要由兴奋性和抑制性突触的突触衰减动力学。然而，我们的初步分析，在体内膜电压波动记录在第二层V1锥体细胞，表明波动具有正偏态分布（即非高斯）和远低于预期的功率在高频率下从过滤建立通过突触动力学或膜充电时间。考虑到电压波动在皮层动力学和计算模型中的核心作用， 这对于理解体内波动的性质以及我们关于电压分布和频谱的新观察如何影响皮层神经元的输入输出功能至关重要。为了解决这些问题，该项目将分析体内膜电压波动，并使用我们的动态钳软件套件中开发的一套新的工具包对其生成进行建模。然后，我们将联合收割机结合我们的模拟突触活动与动态钳注入这些形式的背景活动的神经元在切片制备的第二层V1细胞的评估输入输出功能。