Role of cortical connections to higher-order thalamic nuclei in visual decision-making

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PROJECT SUMMARY To guide decisions, visual information must flow from primary visual cortex (V1) to prefrontal cortex (PFC), via multiple, parallel cortico-cortical and cortico-thalamo-cortical connections. Both V1 and PFC have direct connections with the pulvinar, a higher-order nucleus of the thalamus, but the role of this nucleus in sensory processing is still largely mysterious. Importantly, much of the pulvinar has no homologue in rodents or carnivores, which makes studying it in nonhuman primates all the more important. This goal of this project is to uncover how direct connections between the cortex (V1 and PFC) and the pulvinar interact and impact visual perception and visually-guided decisions in non-human primates. To achieve this goal, the project proposes a novel method, using focused ultrasound to non-invasively open the blood brain barrier, in order to precisely target cortico-thalamic projections for causal, optogenetic manipulations. Current evidence points to a critical role for the pulvinar in redirecting visual attention, but its role in visually-guided decision-making and perception is less clear. To directly test how these cortico-thalamic projections affect visual perception and decision-making, these circuits will be optogenetically activated while monkeys perform challenging psychophysical tasks. We will then be able to assess the contribution of individual, cell-type specific, components of these circuits, by measuring changes in behavioral performance and differences in neural responses across multiple brain areas. The proposed projects builds on my experience implementing multi-area electrophysiological recordings and optogenetic manipulations in awake, behaving primates. The training phase will allow me to develop novel approaches for transfecting larges areas with optogenetic constructs and practice targeting deep thalamic structures in the primate brain electrophysiologically. The long-term goal for my research program is to resolve the essential neural circuit that sensory information must pass through in order to become available for perceptually-based decisions. The central hypothesis for this is work is that cortical-thalamic loops are necessary for the subjective experience of sensory inputs, and a fundamental feature of perceptual decision-making. My goal is to apply this circuit-level knowledge of perceptual representations to improve brain function in the disease state or following damage to sensory organs, but also to use this knowledge to improve how we can effectively communicate information to healthy brains.