Synaptic basis for visual cortical receptive field properties

描述(申请人提供)：哺乳动物的新大脑皮层调节各种认知功能，了解皮层处理的电路基础是神经科学的中心目标。在初级视觉皮质(V1)，单个神经元的感受野特性已被广泛描述，但潜在的神经元回路仍不清楚。这项研究的目的是剖析V1神经元时空感受野背后的兴奋性和抑制性突触输入。在实验上，我们将在麻醉的大鼠和猫身上进行细胞内(膜片钳)记录，以测量皮质神经元的突触输入。在计算上，我们将应用线性和非线性分析来确定每个输入的接受场属性。有四个具体目标。目的1是描述简单细胞基本感受野和方向选择性背后的突触机制。为了测试反相抑制模型，我们将确定兴奋性和抑制性感受场在多大程度上相互匹配，具有相反的开/关极性。将评估几种拟议机制对简单细胞方向选择性的贡献。目标2是描述复杂细胞感受域亚单位下的突触回路。对复杂单元RFS的不同电路模型的预测将进行测试。我们还将确定几种拟议的机制对复杂细胞方向选择性的贡献。在目标3和目标4中，我们将讨论处理运动刺激时涉及的两个更高级的接受场特性。我们最近使用细胞外记录进行的研究表明，V1神经元的方向选择性输入存在空间不对称，这导致了两种新的射频特性，可以解释两种视觉错觉。在目标3中，我们将检查方向选择性兴奋和抑制输入的空间分布，以测试和约束非对称电路模型。在目标4中，我们将测量运动适应对兴奋性和抑制性突触输入的强度和方向选择性的影响，以确定这些输入如何在适应诱导的V1方向选择性改变中起作用。为了进一步检验非对称电路模型，我们还将测量运动适应对兴奋性和抑制性输入的空间分布的影响。这种对皮层感受野特性的突触机制的全面描述不仅对理解V1功能至关重要，而且可能有助于阐明皮质计算的一般原理。公共健康相关性皮层兴奋和抑制之间的平衡对正常的大脑功能至关重要，平衡的破坏会导致各种精神障碍。这项拟议的研究旨在了解兴奋性和抑制性输入之间的关系，以及它们如何塑造视觉皮质神经元的功能特性。这些知识不仅对开发治疗视觉功能缺陷至关重要，而且对癫痫等其他神经疾病的治疗也是至关重要的。

DESCRIPTION (provided by applicant): The mammalian neocortex mediates a variety of cognitive functions, and understanding the circuit basis for cortical processing is a central goal in neuroscience. In the primary visual cortex (V1), the receptive field properties of individual neurons have been characterized extensively, but the underlying neuronal circuitry remains unclear. The goal of the proposed research is to dissect the excitatory and inhibitory synaptic inputs underlying the spatiotemporal receptive fields of V1 neurons. Experimentally, we will make intracellular (patch clamp) recordings in anesthetized rats and cats to measure the synaptic inputs to cortical neurons. Computationally, we will apply both linear and nonlinear analyses to determine the receptive field properties of each input. There are four specific aims. Aim 1 is to characterize the synaptic mechanisms underlying the basic receptive field and direction selectivity of simple cells. To test the anti-phase inhibition model, we will determine the extent to which the excitatory and inhibitory receptive fields are matched to each other with opposite ON/OFF polarities. The contributions of several proposed mechanisms to simple cell direction selectivity will be assessed. Aim 2 is to characterize the synaptic circuitry underlying the receptive field subunits of complex cells. The predictions of different circuit models for complex cell RFs will be tested. We will also determine the contributions of several proposed mechanisms to complex cell direction selectivity. In Aims 3 and 4 we will address two of the more advanced receptive field properties involved in processing motion stimuli. Our recent study using extracellular recordings indicated a spatial asymmetry in direction-selective inputs to V1 neurons, which gives rise to two novel RF properties that could account for two visual illusions. In Aim 3, we will examine the spatial distributions of direction-selective excitatory and inhibitory inputs in order to test and constrain the asymmetric circuit model. In Aim 4, we will measure the effects of motion adaptation on the strength and direction selectivity of excitatory and inhibitory synaptic input to determine how these inputs contribute to adaptation-induced change in V1 direction selectivity. To further test the asymmetric circuit model, we will also measure the effect of motion adaptation on the spatial distributions of the excitatory and inhibitory inputs. Such comprehensive characterization of the synaptic mechanisms underlying cortical receptive field properties is not only crucial for understanding V1 functions, but also likely to shed light on the general principles of cortical computation. PUBLIC HEALTH RELEVANCE Balance between excitation and inhibition in the cortex is critical for normal brain functions, and disruption of the balance causes a variety of mental disorders. The proposed research aims to understand the relationship between excitatory and inhibitory inputs, and how they shape the functional properties of visual cortical neurons. Such knowledge will be crucial for the development of treatment for not only deficiencies in visual functions, but also other neurological disorders such as epilepsy.