The aim of this proposal is to identify the underlying intrinsic mechanisms of contextual modulation in primary visual cortex (V1). Though the basic drive of orientation selectivity of V1 neurons is known to derive from retinal relays of the lateral geniculate nucleus (LGN), modulation of this classical receptive field (CRF) is generated through lateral long-range connections within V1. This surround modulation can either suppress or enhance the response of a neuron to its CRF. Previous work from the Sur lab and others has shown that the direction of the modulation depends on the orientation of the surround and the contrast of the CRF. Furthermore, orientation preference maps are arranged so that transitions between preferred orientation domains can be smooth or fractured (where incongruent orientation domains are found adjacent to each other). There are indications that long-range inputs to these fracture sites come from an in-homogenous array of other orientation domains, whereas smooth, or iso-orientation domains are known to receive lateral connections primarily from like iso-orientation domains. The proposed experiments will use optical imaging to identify fracture sites for fluorescent tracer injections, and two-photon microscopy will be used to identify the resulting clusters of labeled cells in V1. By matching the sites of labeled cells with the orientation preference map we can define specifically which regions provide modulatory input. With this information we can discreetly stimulate these regions with optimal orientation displays and systematically measure the effects on the CRF.