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.