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

描述（由申请人提供）：尖峰速率或时间的变化是神经元反应的基本输出特征。然而，神经元尖峰输出具有噪声或随机性的特点，因此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活动时，皮层神经元放电尤其如此。在某种程度上，脉冲放电的随机性与膜电压波动的潜在性质有关，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-输出响应上。通常，突触活动的嘈杂波动被认为是“背景”活动，它调节神经元如何对仅由少数积极参与单一刺激的突触前神经元提供的确定性输入做出反应。例如，背景电压波动被认为增加了视觉皮质神经元对弱输入的敏感性，从而提供了一种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化为尖峰输出中起着根本作用。为了解决这些问题，以前的建模工作假设膜电压波动可以用正态（高斯）分布来描述，其功率谱在很大程度上取决于兴奋性和抑制性突触的突触衰减动力学。然而，我们对第II层V1锥体细胞中记录的体内膜电压波动的初步分析表明，波动具有正偏态分布（即非高斯分布），并且在高频率下的功率远低于通过突触动力学或膜充电时间建立的滤波所期望的功率。鉴于电压波动在皮质动力学和计算模型中的核心作用，它是

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.