PROJECT SUMMARY Before visual signals from the eye reach the cortex, they are processed by two powerful inhibitory networks in the thalamus. First, local interneurons within the dorsal lateral geniculate nucleus (dLGN) provide feedforward inhibition to relay cells and each other. Second, the thalamic reticular nucleus (TRN) receives input from relay cells and inhibits them in return. These basic circuit elements are repeated across primary thalamic nuclei in most mammals, including humans. Characterizing inhibitory networks in the dLGN is, thus, key to understanding the early visual pathway as a whole and the thalamus in particular. Further, understanding how healthy brains work provides a basis to help diagnose disorders and restore function in disease. Here we explore intrinsic circuits in the thalamus by recording from interneurons themselves and the inhibition they supply to relay cells during vision, using an interdisciplinary approach that combines different experimental techniques with custom computational methods. The proposal is divided into three aims. Aim 1 asks how visual responses in the TRN are derived and how this structure influences dLGN. Our past work showed that receptive fields in the cat visual TRN are selective for specific elements of the visual scene and operate over local spatial scales; these results are consistent with roles in feature processing and spatial attention. Recent studies of attention in mouse, and our own preliminary results, suggest that the TRN may play the same roles in rodents as in carnivores and primates. Thus, we will continue our studies of TRN in mouse, a tractable preparation in which reticular cells can be located and manipulated optogenetically. Aim 2 focuses on local interneurons in the dLGN. We will map their receptive fields and explore their tuning for stimulus attributes such as direction of motion, orientation and size in order to delineate the inhibitory mechanisms that contribute to feature selectivity in relay cells. Subsequently, we will use optogenetic tools to suppress interneurons and ask how the loss of their input impairs stimulus selectivity in relay cells. Last, Aim 3 uses comparative approaches to highlight structural and functional strategies that brains use to interpret the environment. For example, push-pull excitation and inhibition are present in retinal ganglion cells from mouse to monkey and in relay cells of every species we test: this synaptic arrangement seems key to form vision. Yet, our preliminary results suggest that the visual response properties of the interneurons that supply inhibition to relay cells differ, not only between cat and mouse, but even between animals in the same taxonomic order, cats and ferrets. We will use simple computational models to understand how different inhibitory circuits can achieve common functional outcomes. Our belief is that comparative approaches are crucial for relating research done in one species to another and, ultimately, for understanding human visual processing.