To date no unitary theory of cortical function has emerged despite a long history of cortical research. Single cell approaches in primary visual cortex, as exemplified by Hubeland Wiesel's studies and by recent work on parallel visual pathways, have produced functional circuit diagrams arguing for hierarchical, feedforward processing. Alternatively, artificial neural network research argues that the cortex might represent a distributed feedback circuit in which intrinsic dynamics converge in stable states that represent computational solutions. these two types of models predict very different activation patterns of the circuit. The goal of the research is to elucidate the three-dimensional spatio-temporal activity patterns intrinsic to the cortical microcircuit and to identify their underlying circuits. Studies will be carried out with brain slices from mouse visual cortex using calcium imaging with a cooled CCD camera, a photodiode array and two-photon microscope. These techniques allow the investigators to follow the activity of neuronal ensembles across the entire slice with single-cell and submillisecond resolution. Specifically, the investigators will (i) determine the three-dimensional activity patterns present in a brain slice (ii) establish the anatomical and functional connectivity underlying these dynamics and (iii) identify neurons playing key roles and study their effect in altering circuit dynamics. These studies may help determine whether cortical neurons can activate in preferential labeled lines, as predicted by feedforward models or in a widely distributed pattern, as predicted by feedback models, shedding light on the functional units of cortical microcircuitry and their co-ordination in cortical function as a whole. Finally, they will help understand the central pathophysiological consequences of amblyopia and strabismus, as well as help design therapeutic strategies aimed at compensating for these defect. A more complete understanding of the circuitry will also improve the analysis of visual evoked potentials (VEP) and thus the measurement of acuity, contrast sensitivity and chromatic sensitivity of preverbal children and in early diagnosis of visual pathologies.
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