Distinct cell types in the visual cortex contribute in unique ways to cortical circuits and function. Furthermore, the location of cortical cells within maps enables them to have specific functions. We propose to use state-of-the-art tools to examine the role of specific cell types in visual cortex circuits in vivo. First, we will examine how neurons in ferret visual cortex simultaneously map multiple response features at single cell resolution, using two-photon imaging of calcium signals. We hypothesize that neuronal representations maximize continuity and coverage by creating precise representations of response features that contain spatially offset regions of high and low rates of change. Second, we will examine the response characteristics and mappings of neuronal populations which project to specific cortical targets. We will use retrograde labeling of fluorescent tracers combined with two-photon imaging to compare response features and representations of neurons that project to area PSS, and hence to a putative motion-processing stream, with neurons that project to area 21, and hence to a putative form- processing stream. Third, we will compare the responses of inhibitory neuron subpopulations in ferret V1 recorded with high resolution imaging in vivo and subsequently identified by immunohistochemical markers ex vivo, and examine the hypothesis that specific inhibitory neuron subsets have distinct response features and tuning. We will examine the response features of inhibitory neuron subpopulations in mouse V1 marked by a genetic cre-lox system, and examine the hypothesis that parvalbumin- and calretinin-expressing interneurons have distinct response properties. In addition, we will examine the function of these interneuron types in mice with selective genetic deletion of one subpopulation or the other, in which we predict particular influences on response features of excitatory neurons. Fourth, we will examine whether individual neuronal dendrites show integrative responses, which are summed and thresholded at the soma to impart unique responses to neurons. We will examine response features of individual dendrites and dendritic compartments of single neurons in ferret V1 that have specific projections such as to area PSS and area 21. We will examine their dendritic responses by labeling with either (a) intracellular injection of calcium indicator dye, or (b) a novel genetically engineered CaMKII1 FRET probe, and compare responses to those at the soma recorded by visualized whole-cell patch recording. Together, we expect these studies to contribute significantly to an understanding of how specific cell types in visual cortex contribute to cortical function, and thus how cortical dysfunction might arise from diseases that target a particular type of cell.
Significance Distinct populations of neurons contribute to the development and function of neural circuits for vision;the precise organization of these cell populations and integration of their inputs within cortical area V1 is necessary for the establishment of coherent internal representations of visual stimuli. This project aims to explore the integrative properties of visual cortex on spatial scales ranging from individual dendrites to neural networks, identifying vectors of visual system dysfunction and targets for their intervention.
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