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中起着至关重要的作用，这在很大程度上可能是由活动依赖性突触修饰介导的。虽然在每个层面-突触，电路和功能-皮层可塑性已被广泛研究，活动诱导的修改之间的因果关系在不同的水平仍然是牢固地建立。我们的目标是在这些水平上架起理解皮层可塑性的桥梁。在最近的研究中，我们已经证明，异步视觉刺激（1-2分钟）可以诱导成人皮层感受野（RF）和人类空间感知的变化与尖峰时间依赖性可塑性（STDP），一个强大的突触学习规则广泛观察到兴奋性突触在大脑中一致的方式。在拟议的研究中，我们将进一步研究STDP介导的成人视觉皮层的功能修改，使用电生理和心理物理实验和计算建模相结合。本研究的主要目的有三：探讨大脑皮层可塑性的机制和功能意义。在目标1中，我们将测试RF和知觉的修改是否可以通过短期（秒）的视觉条件反射，最近的研究表明，在皮层切片的可能性。这种快速的可塑性可能在自然条件下更频繁地运作，本实验将为我们后续研究自然刺激诱导的皮层修饰提供基础。在目标2中，我们将研究功能修饰背后的神经元回路。我们将首先测量该效应的眼间转移，以确定其是否起源于皮质。然后，我们将系统地研究皮层修改对条件反射参数（方向，亮度极性，时间和条件反射刺激的位置）和记录的神经元的其他属性（简单/复杂分类，层状位置，双眼和方向选择性）的依赖性，以进一步确定潜在的电路。在目标3中，我们将通过测量由运动刺激和包含运动信号的自然场景引起的皮层修改来直接评估可塑性的功能相关性。总之，这些研究很可能提供重要的新见解的功能影响的活动依赖性突触可塑性在皮层电路，射频特性和视觉感知的水平。

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.