Cortical mechanisms mediating visual function and behavior

描述（由申请人提供）：在过去的四十年中，来自麻醉动物感觉皮层的细胞内记录对我们理解皮层处理做出了重大贡献，为形成单个皮层神经元尖峰响应的突触输入提供了一个窗口。然而，到目前为止，细胞内记录尚未应用于清醒的行为灵长类动物。通过结合我们两个实验室的独特专业知识，我们最近开发了新的技术，使我们能够在常规基础上，在清醒的行为猴子的初级视觉皮层（V1）中进行可靠的全细胞细胞内记录。这是第一次，我们可以同时获得单个皮层神经元的阈下（代表输入的膜电位）和阈上（代表输出的尖峰）反应，同时还可以利用视觉刺激的精确控制和神经元的功能。 受试者的行为状态由行为灵长类动物提供。我们在清醒的行为灵长类动物中进行细胞内记录的能力为解决两个基本问题打开了大门，这两个问题与介导视觉感知的回路水平机制有关：（1）单个皮层神经元的阈下和阈上活动与感知决策之间的关系是什么，以及（2）感觉皮层中自上而下的注意力调节的潜在机制是什么。为了解决这些问题，我们将首先研究单个V1神经元的阈下和阈上反应的变异性与猴子执行要求苛刻的视觉检测任务（目标1）的感知决策的变异性之间的定量关系。在目标2中，我们将研究如何通过改变刺激呈现的注意力状态来改变阈下和阈上反应。我们目前的初步数据表明，这些记录不仅在技术上是可行的，但也能够提供重要的和独特的见解的细胞和电路水平的机制，介导皮层感觉处理。

DESCRIPTION (provided by applicant): Over the past four decades, intracellular recordings from sensory cortex of anesthetized animals have made major contributions to our understanding of cortical processing, providing a window into the synaptic inputs that shape spiking responses of individual cortical neurons. To date, however, intracellular recording has not been applied in awake, behaving primates. By combining the unique expertise from our two laboratories, we have recently developed novel techniques that allow us to conduct, on a routine basis, reliable, whole-cell intracellular recordings in primary visual cortex (V1) of awake, behaving monkeys. For the first time, we have access to both subthreshold (membrane potentials representing input) and suprathreshold (spikes representing output) responses of individual cortical neurons, while also utilizing the precise control of visual stimulation and the subject's behavioral state afforded by behaving primates. Our ability to perform intracellular recordings in awake, behaving primates opens the door to addressing two fundamental questions with respect to the circuit-level mechanisms that mediate visual perception: (1) what is the relationship between sub- and supra-threshold activity of single cortical neurons and perceptual decisions, and (2) what are the underlying mechanisms of top-down attentional modulations in sensory cortex. To address these questions, we will first study the quantitative relationship between variability in sub- and suprathreshold responses of single V1 neurons and variability in perceptual decisions of monkeys performing a demanding visual detection task (Aim 1). In Aim 2, we will examine how sub- and suprathreshold responses are altered by changing the attentional state under which the stimulus is presented. We present preliminary data demonstrating that these recordings are not only technically feasible, but are also able to provide important and unique insights into the cellular and circuit-level mechanisms that mediate cortical sensory processing.