Dynamic Properties of Visual Cortical Circuits

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Description (provided by applicant): The inhibitory circuits of the visual thalamus dominate local processing and influence all information that relay cells transmit from the eye to the brain. These circuits divide into two major groups based on position in the visual pathway. Local interneurons in the main layers of the lateral geniculate nucleus receive input from the retina and provide feedforward inhibition to relay cells and each other. The perigeniculate sector of the reticular formation is innervated by relay cells and feeds back inhibition to these cells in turn. Despite the importance of these suppressive networks to vision, little is known about how they operate in situ. The proposed research addresses this gap by investigating inhibitory cells in the perigeniculate and lateral geniculate nuclei using an interdisciplinary approach that combines intracellular recording from identified interneurons and extracellular multiunit recording with computational analysis and modeling. Aim 1) How do the spatiotemporal receptive fields of relay cells and local interneurons compare? Relay cells have receptive fields built from concentric On and Off subregions with a push-pull layout of excitation and inhibition; where bright stimuli excite, dark inhibit and vice versa. The excitation (push) comes from retinal ganglion cells whose receptive fields have the same location and center sign (On or Off) as that of the target relay cell. This aim tests the hypothesis that the inhibition (pull) is routed through interneurons driven by ganglion cells whose fields have similar positions but the opposite sign as that of the target relay cell. Aim 2) Do relay cells and local interneurons sample and integrate feedforward input the same way? Many thalamic neurons receive input from more than one ganglion cell. This aim asks how retinothalamic convergence redraws the map of visual space laid out in the eye. Additional experiments explore how previously established disparities between the anatomy and pharmacology of relay cells vs. interneurons produce commensurate differences in synaptic integration. Aim 3) Does feedback inhibition from the perigeniculate nucleus operate over multiple spatial scales? The perigeniculate nucleus is widely believed to regulate global levels of activity rather than to play a spatially targeted role in visual processing. Yet, mounting evidence counters this simple view. This aim explores circuits that build reticular receptive fields and investigates the possibility that these fields range widely in size, even at the same position in the visual field. SIGNIFICANCE: Knowledge of how the healthy brain operates provides a standard against which to judge changes that result from various disorders, as well as a model system for testing drugs developed to treat illness. Thus, understanding how inhibitory circuits in the thalamus normally function is necessary to identify mechanisms that go awry during disease. For example, this project bears directly on a key theme in research on amblyopia, the examination of how abnormal visual experience leads to changes in central processing. PUBLIC HEALTH RELEVANCE: This project investigates feedforward and feedback inhibitory circuits in the visual thalamus. Understanding how thalamic circuits function in the healthy brain is necessary to identify mechanisms that go awry during disease. For example, the work proposed here bears directly on a key theme in research on amblyopia, the examination of how abnormal visual experience leads to changes in central processing.