Functional Plasticity in Adult Visual Cortex

描述（由申请人提供）：活动依赖性可塑性对神经系统的发育和功能至关重要。在哺乳动物的新皮层中，感觉刺激在形成回路和功能方面起着至关重要的作用，这可能主要是由活动依赖性突触修饰介导的。尽管在突触、电路和功能等各个层面的皮层可塑性已经得到了广泛的研究，但在不同层面上活动诱导的修饰之间的因果关系仍有待确立。我们的目标是在这些层面上建立对皮质可塑性的理解。在最近的研究中，我们已经证明了异步视觉刺激（1-2分钟）可以诱导成人皮层接受野（RFs）和人类空间感知的转变，其方式与spike- time -dependent plasticity （STDP）一致，STDP是一种在大脑兴奋性突触中广泛观察到的强大的突触学习规则。在本研究中，我们将采用电生理、心理物理实验和计算模型相结合的方法，进一步研究STDP介导的成人视觉皮层功能改变。研究皮层可塑性的机制和功能意义有三个具体目的。在目的1中，我们将测试是否RF和知觉改变可以由短时间（秒）的视觉条件反射诱导，这是最近在皮质切片研究中提出的一种可能性。这种快速的可塑性可能在自然条件下更频繁地发生，本实验将为我们后续研究自然刺激引起的皮质修饰提供基础。在目标2中，我们将研究功能修饰背后的神经回路。我们将首先测量这种效应的眼间转移，以确定它是否起源于皮层。然后，我们将系统地检查皮质修饰对条件反射参数（方向、亮度极性、时间和条件反射刺激的位置）和记录神经元的其他属性（简单/复杂分类、层流位置、双眼性和方向选择性）的依赖性，以进一步确定潜在的电路。在Aim 3中，我们将通过测量运动刺激和包含运动信号的自然场景引起的皮质修饰，直接评估可塑性的功能相关性。总之，这些研究可能为皮层回路、射频特性和视觉感知水平上活动依赖性突触可塑性的功能含义提供重要的新见解。

DESCRIPTION (provided by applicant): Activity-dependent plasticity is essential for development and function of the nervous system. In the mammalian neocortex, sensory stimuli play crucial roles in shaping the circuitry and function, which may be largely mediated by activity-dependent synaptic modification. Although at each level - synaptic, circuitry, and functional - cortical plasticity has been studied extensively, the causal relationship between activity-induced modifications at different levels remains to be firmly established. Our goal is to bridge the understanding of cortical plasticity at these levels. In recent studies, we have demonstrated that asynchronous visual stimuli (1-2 min) can induce shifts in adult cortical receptive fields (RFs) and in human spatial perception in a manner consistent with spike-timing-dependent plasticity (STDP), a powerful synaptic learning rule widely observed among excitatory synapses in the brain. In the proposed study we will further examine the functional modifications of adult visual cortex mediated by STDP, using a combination of electrophysiological and psychophysical experiments and computational modeling. There are three specific aims, examining the mechanism and functional significance of the cortical plasticity. In Aim 1, we will test whether RF and perceptual modifications can be induced by brief periods (seconds) of visual conditioning, a possibility suggested by recent studies in cortical slices. Such rapid plasticity may operate more frequently under natural conditions, and this experiment will provide a basis for our subsequent studies of cortical modifications induced by natural stimuli. In Aim 2, we will investigate the neuronal circuitry underlying the functional modification. We will first measure the interocular transfer of the effect to determine whether it is cortical in origin. We will then examine systematically the dependence of the cortical modification on conditioning parameters (orientation, luminance polarity, timing, and location of conditioning stimuli) and on other properties of the recorded neuron (simple/complex classification, laminar location, binocularity, and direction selectivity) to further determine the underlying circuitry. In Aim 3, we will directly assess the functional relevance of the plasticity by measuring cortical modification induced by motion stimuli and by natural scenes containing motion signals. Together, these studies are likely to provide significant new insights into the functional implications of activity-dependent synaptic plasticity at the levels of cortical circuitry, RF properties, and visual perception.