Wednesday, February 5, 2025
2/5/2025
Corticothalamic circuits linking the primary sensory cortex with the primary sensory thalamus in the feedback direction are ubiquitous across sensory modalities and mammalian species and are ideally positioned to regulate the flow of sensory signals from periphery to cortex. However, the functional role of these circuits in sensory perception remains a fundamental mystery in neuroscience. In the visual system, corticogeniculate neurons provide the majority of inputs onto neurons in the dorsal lateral geniculate nucleus (LGN), however receptive fields of LGN neurons closely resemble their retinal inputs and not their corticogeniculate inputs. Partly because corticogeniculate influence over LGN activity is modulatory rather than driving, the functional role of corticogeniculate feedback in vision has been difficult to characterize. The overarching goal of this proposal is to elucidate the structural organization of corticogeniculate feedback and its functional role in visual perceptual behavior. To accomplish this goal, intersecting and emerging technologies are employed including functional ultrasound imaging, neurophysiological recording, optogenetics, and chemogenetics in two highly visual mammalian species: ferrets and macaque monkeys. Building upon our previous findings that corticogeniculate feedback regulates the timing and precision of LGN responses to visual inputs, the three Specific Aims of this proposal address important new questions regarding the function and connectivity of corticogeniculate feedback. Specific Aim 1 will examine whether corticogeniculate feedback regulates the temporal dynamics of LGN neurons uniquely, depending on the type of visual feature information they convey. Specific Aim 2 will examine the spatial extent of corticogeniculate influence over LGN population activity using a combination of functional ultrasound and optogenetics. Aim 2 will also examine the precise functional connectivity between individual corticogeniculate and LGN neurons to determine whether corticogeniculate circuits exert stream-specific influence on individual LGN neurons. A major motivation behind Specific Aims 1 and 2 is to determine whether corticogeniculate feedback regulates visual information transmission through the LGN in a stream-specific manner or whether corticogeniculate influence is more global and diffuse. Specific Aim 3 represents a significant step forward in understanding corticogeniculate function by testing how corticogeniculate circuits contribute to visual discrimination behavior. We have developed a novel virus-mediated gene delivery strategy that enables selective manipulation of corticogeniculate circuits via optogenetics or chemogenetics, applicable to long-term behavioral experiments in ferrets. Together, results of the experiments proposed under each Aim will provide a fuller picture of the functional role of corticogeniculate feedback in visual perception by revealing the underlying connectivity and mechanisms giving rise to these functions. Importantly, insights gained about corticogeniculate circuit function could generalize across corticothalamic and corticocortical pathways throughout the sensory system and inform understanding of sensory circuit disruptions associated with many neurological disorders.
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