DESCRIPTION (provided by applicant): The cerebral cortex of mammals has the ability to control and modulate innate, reflexive behaviors mediated by subcortical structures. By adjusting innate and reflexive behaviors to the prevailing conditions or by adapting these behaviors according to past experiences the cortex greatly expands the behavioral repertoire of mammals. Despite the fundamental role that the cortex plays on regulating subcortically mediated behaviors very little is known about the underlying mechanisms. Solving this problem is crucial for our understanding of among the most basic functions performed by the cerebral cortex of mammals. This proposal addresses the mechanisms by which the cortex modulate the performance of the optokinetic reflex, an innate behavior that is essential for stabilizing images on retinas during slow self motions or motions of the environment. The proposed study will be performed in mice because of the large palette of genetic, viral, optical and electrophysiological tools especially developed to study neural circuit function in this animal. In humans, both developmental retardation of the visual cortex as well as lesions or strokes to the visual cortex can profoundly impair optokinetic performance. Optokinetic performance is part of the standard neurological tests in the medical practice because of its simplicity and diagnostic power with regard to subcortical and cortical function. Understanding the fundamental mechanisms that regulate the various properties of optokinetic performance will inevitably contribute to the expansion of the diagnostic power of this simple and widely used neurological test on human patients. The ability of cortex to control subcortically mediated innate behaviors represents a fundamental evolutionary adaptation. This control becomes particularly pronounced in organisms with high levels of encephalization, humans being the supreme example. Revealing the circuit mechanisms through which the cortex controls the activity of subcortical structures will provide crucial insight into how the cortex orchestrates innate behavior in health and disease.