Understanding how circuits in visual cortex transform the information supplied by different populations of retinal ganglion cells into orderly representations of the visual world remains a fundamental challenge that limits our progress in elucidating the cortical mechanisms of visual perception. While progress has been substantial, a major gap in our understanding of the cortical transform remains because the transform ultimately resides in the input/output functions of individual neurons, and the functional synaptic architecture that allows individual neurons to integrate inputs from diverse sources to produce coherent sensory representations remains largely unknown. The experiments in this proposal address this challenge by employing state of the art in vivo functional imaging techniques to probe the functional synaptic architecture of columnar representations in layer 2/3 of primary visual cortex (V1). Recent work from this laboratory has provided new insights into how the information derived from ON- and OFF- center retinal ganglion cells is transformed into orderly columnar maps of orientation, visual space, and absolute spatial phase in layer 2/3 of the tree shrew, a species that has a close phylogenetic relation to primates and a well-developed functional columnar architecture. The goal of the proposed experiments is to elucidate the functional synaptic architecture of this cortical transform by using in vivo 2-photon imaging of calcium signals to visualize the response properties of identified synaptic inputs within the dendritic fields of individual layer 2/3 pyramidal neurons.
Two specific aims are proposed, one focused on elucidating the synaptic architecture of the receptive field center and the other, the synaptic architecture of the receptive field surround. These experiments will provide the first detailed test of the functional specificity of synaptic inputs that a neuron receives and how these inputs compare with the properties of the receptive field center and surround. Equally important, these experiments will determine the spatial organization of functionally defined synaptic inputs within the dendritic tree, providing the first direct test of the hypothesis that dendritic topology contributes significantly to somatic receptive field structure. By taking advantage of a novel model system, and the latest advances in in vivo imaging and genetically encoded calcium sensors, these experiments will yield a host of novel insights into the functional synaptic architecture of the cortical transform that will enlighten our understanding of mechanisms of cortical function and their alteration in injury and disease.
Projective Narrative The proposed experiments will use state of the art imaging techniques to provide new insight into the functional organization of cortical circuits that is critical for addressing numerous visual, neurological, and psychiatric disorders that are grounded in cortical circuit dysfunction.
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