Project Summary / Abstract A long-term goal of our research is to understand how cortical neurons become tuned to stimulus features and organized into cortical maps. Our working hypothesis is that the spatial distribution of ON/OFF inputs from the geniculate seeds simple-cell receptive fields, cortical columns, and maps. This hypothesis stands in stark contrast with the textbook account that cortical receptive fields and maps develop through self- organizing processes driven by structured, spontaneous activity in the LGN. To test our hypothesis, we seek to investigate predicted correlations between the organization of the thalamocortical projection and the receptive fields and tuning of cortical neurons. In Aim 1, we seek to determine if there is a link between the spatial layout of ON/OFF domains, receptive field structure, and tuning in primary visual cortex. In Aim 2 we will classify and cluster thalamocortical boutons according to their responses to a rich set of visual stimuli, allowing us to reconstruct the tiling of the visual field by different classes of geniculate neurons. We will then study the spatial distribution and clustering of geniculate afferents into the cortex. Finally, in Aim 3, we will investigate a predicted correlation between the organization of thalamocortical projections and cortical organization in single animals. We will achieve this by simultaneously imaging the activity of thalamic boutons and cortical neurons using dual-color imaging. The proposed studies are significant as they test the possibility that an imbalance between the ON and OFF responses from the periphery provides a scaffold for the development of simple cell receptive fields and cortical columns. A positive outcome would prompt a revision of our current views of the development of the cortical architecture.