The integration of sensory and motor systems is perhaps the most fundamental achievement of nervous systems and a topic of broad interest in neurobiology. One essential feature of this integration is the ability of nervous systems to distinguish the sensory stimulation generated by an organism's own movements from externally induced stimulation. In this application, a circuit model is proposed to explain how the visual stimulation resulting from the rapid movement of the visual field that occurs during a saccadic eye movement is attenuated to prevent both perceptual blurring and the triggering of unwanted subsequent saccades. The model hypothesizes premotor cells located in the intermediate layer of the superior colliculus that command saccades give rise to local axonal collaterals that activate neighboring GABAergic inhibitory neurons. The model also hypothesizes that these intermediate layer GABAergic neurons inhibit visuosensory neurons in the superficial layer of the superior colliculus. The goal of this application is to test this model using a combination of in vitro anatomical and physiological techniques. Our first Specific Aim is to determine whether the intermediate layer GABAergic cells that project to the superficial layer receive excitatory input from neighboring premotor cells. The second Specific Aim is to determine whether the visuosensory cells in the superficial layer that receive the GABAergic input project to the underlying premotor cells and to thalamocortical relay cells in the visual thalamus. During saccades, this GABAergic pathway would attenuate the inputs to both the premotor cells and the visual areas of the cortex. Neurons in the superficial and intermediate layers will be identified either by GFP fluorescence in GAD 67-GFP knock-in mice or with retrograde tracers injected in the destinations of their axons. Their synaptic responses to intra- and intralaminar photostimulation of presynaptic cells will be measured by whole-cell patch clamp recordings. In addition to testing at the cellular level a circuit model for a fundamental property of visuomotor systems, these experiments will deepen our understanding of the structure and functions of the intra- and interlaminar circuitry of the superior colliculus. Understanding the normal circuitry will allow us to develop rational hypotheses to explain dysfunctional sensorimotor behavior associated with disease. ? ? ?
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