Cellular Mechanisms of Visual Cortical Function

描述（由申请人提供）：大脑皮层的基本操作，一个大规模和动态互连的皮层神经元和网络，关键取决于单个细胞兴奋性的快速调节，允许它们参与或不参与当前活跃的神经网络，以响应行为和上下文需求。这种快速增益调制反映在动作电位的数量和时间的变化中。使用初级视觉皮层作为模型系统，我们将研究控制皮层神经元反应的突触和网络机制，特别关注自然主义的视觉输入（自然电影）。为了彻底理解增益调制，我们将首先研究对比度响应函数曲线的细胞机制，作为皮质输入-输出关系的典型例子。这些研究将检查阈值响应、中等范围灵敏度和高对比度下饱和度的起源。一旦理解了这种原型关系的细胞机制，我们将操纵单个视觉皮层神经元的膜电位、输入电导和膜方差（以及刺激非经典感受野），以确定这些因素如何影响对比度响应函数曲线。这些增益调制研究将与旨在揭示控制反应时间精度和可变性的突触机制的实验相补充。视觉皮层神经元对全视野自然视觉场景（电影）的反应具有时间精确、高度选择性和异常空间动作电位序列。这些反应通常不能很好地预测细胞的经典感受野的线性特性。通过记录在呈现自然刺激的过程中到达视觉皮层神经元的兴奋性和抑制性输入的模式，我们将确定兴奋性，抑制性和尖峰起始特性对尖峰定时精度的贡献。通过改变视觉刺激的大小（包括刺激的非经典的感受野以及经典的感受野），同时记录从V1神经元在不同的膜电位，我们将确定兴奋性和抑制性事件的相对贡献增加动作电位的选择性和稀疏性与自然刺激的反应。这些研究将揭示皮层增益控制、尖峰时间和神经元信号传导的基本机制，并导致对视觉皮层网络功能和功能障碍的更好和更透彻的理解。大脑皮层是人类大脑中最重要的结构，但人们对它的了解还很有限。我们将研究视觉皮层的基本操作原理，以及它如何编码信息，从而实现适当的行为功能。我们的研究将提供与理解有关的基本信息，不仅是视觉，而且还有注意力和记忆力。

Description (provided by applicant): The basic operation of the cerebral cortex, a massively and dynamically interconnected sheet of cortical neurons and networks, depends critically on the rapid modulation of excitability of individual cells, allowing them to participate or not participate in currently active neural networks, in response to behavioral and contextual demands. This rapid gain modulation is reflected in the change in the number and timing of action potentials. Using the primary visual cortex as a model system, we will examine the synaptic and network mechanisms that control the responsiveness of cortical neurons on a moment-to-moment basis, with particular attention to naturalistic visual input (natural movies). To understand gain modulation thoroughly, we will first investigate the cellular mechanisms of the contrast response function curve, as a prototypical example of a cortical input-output relationship. These studies will examine the origins of threshold responsiveness, mid-range sensitivity, and saturation at high contrast. Once the cellular mechanisms of this prototypical relationship are understood, we will then manipulate the membrane potential, input conductance, and membrane variance of individual visual cortical neurons (as well as stimulate the non-classical receptive field) to determine how these factors affect the contrast response function curve. These gain modulation studies will be complemented with experiments designed to reveal the synaptic mechanisms that control response timing precision and variability. Visual cortical neurons respond to full field natural visual scenes (movies) with temporally precise, highly selective and unusually space action potential sequences. These responses are often not well predicted by the linear properties of cells' classical receptive fields. By recording the pattern of excitatory and inhibitory inputs arriving in visual cortical neurons during presentation of natural stimuli, we will identify the contributions of excitatory, inhibitory, and spike initiation properties to spike timing precision. By varying the size of visual stimuli (to include stimulation of the non-classical receptive field as well as the classical receptive field) while recording from V1 neurons at various membrane potentials, we will determine the relative contributions of excitatory and inhibitory events to increases in action potential selectivity and sparseness associated with responses to naturalistic stimulation. These studies will reveal fundamental mechanisms of cortical gain control, spike timing, and neuronal signaling and lead to a better and more thorough understanding of visual cortical network function and dysfunction. The cerebral cortex is the most important structure of the human brain, yet is only partially understood. We will examine the basic operating principles of the visual cortex and how it encodes information, allowing for proper behavioral function. Our studies will give fundamental information relevant to understanding not only vision, but also attention and memory.