Cortical mechanisms mediating visual function and behavior

描述(申请人提供)：在过去的40年里，来自麻醉动物感觉皮质的细胞内记录为我们理解皮质处理做出了重大贡献，为了解突触输入形成单个皮质神经元的尖峰反应提供了一个窗口。然而，到目前为止，细胞内记录还没有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，我们最近开发出了新的技术，使我们能够在常规基础上对清醒、行为正常的猴子的初级视觉皮质(V1)进行可靠的全细胞内记录。我们第一次能够同时获得单个皮层神经元的阈值下(代表输入的膜电位)和阈值上(代表输出的尖峰)反应，同时还利用了对视觉刺激和 受试者的行为状态是由灵长类动物提供的。我们在清醒、行为良好的灵长类动物中进行细胞内记录的能力为解决与调节视觉感知的电路水平机制有关的两个基本问题打开了大门：(1)单个皮质神经元的阈值下和阈值上的活动与感知决策之间的关系，以及(2)感觉皮质自上而下注意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神经元阈值下和阈值上反应的可变性与执行苛刻视觉检测任务的猴子感知决策的可变性之间的定量关系(目标1)。在目标2中，我们将研究如何通过改变刺激呈现的注意状态来改变阈值以下和阈值以上的反应。我们提供的初步数据表明，这些记录不仅在技术上是可行的，而且还能够为调节皮层感觉处理的细胞和电路级机制提供重要和独特的见解。

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.