Corticothalamic circuits linking primary sensory cortex with 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 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 appears to be modulatory rather than driving, the functional role of corticogeniculate feedback in vision has been difficult to characterize. The goal of this proposal is to employ optogenetics ? an emerging technology that allows for selective and reversible manipulation of neurons in intact animals ? to examine the structural organization of corticogeniculate circuits and to elucidate their functional contributions toward vision. The three Specific Aims of this proposal address three critical features of corticogeniculate circuits: 1) the structure-function relationships among corticogeniculate circuits; 2) the types of information conveyed by corticogeniculate neurons to LGN neurons; and 3) how corticogeniculate signals impact LGN neuronal activity. A series of nine experiments, three in each Aim, examining corticogeniculate morphology, physiology, functional connectivity, receptive field transformations and impact on LGN activity, will systematically test two alternative hypotheses that corticogeniculate feedback is functionally homogenous versus functionally stream-specific. To accomplish the experiments under each of the three Specific Aims, corticogeniculate neurons in ferrets are selectively infected with virus encoding channelrhodopsin2 and mCherry and optogenetically activated during simultaneous multi-electrode array recordings of LGN and visual cortical neuronal responses to drifting gratings and white noise stimuli. Preliminary results suggest that optogenetic activation of corticogeniculate neurons is sufficient to drive changes in LGN responses to visual stimuli. In revealing the structural and functional organization of corticogeniculate circuits, the information they convey to the LGN and their impact on LGN activity, results of the proposed experiments will reveal whether corticogeniculate circuits serve as global gain modulators that synchronize activity across LGN cell types or selectively prioritize information about specific visual features through stream-specific modulations. Furthermore, insights gained about corticogeniculate circuit function could generalize across corticothalamic pathways throughout the sensory system and inform understanding of sensory circuit disruptions associated with sensory-processing deficits observed in many neurological disorders.
Corticogeniculate circuits are in a unique position to regulate the feedforward flow of visual signals traveling from the retina to the cortex, however little is known about how corticogeniculate circuits contribute to vision. The experiments proposed aim at elucidating the structural organization of corticogeniculate circuits along with the functional role of corticogeniculate circuits in vision. Optogenetics, an emerging technology, is utilized to identify corticogeniculate neurons and to selectively and reversibly manipulate the activity of corticogeniculate neurons in intact animals. Visual responses of visual thalamic neurons and visual cortical neurons are recorded while corticogeniculate neurons are excited optogenetically in order to identify the physiology, morphology, functional connectivity, and functional contributions of corticogeniculate circuits to visual information processing. Results of this study will provide significant insights into the structure-function relationship of a key sensory pathway and the role of this pathway in sensory perception. Accordingly, results of this study will lay the foundation for understanding how the brain prioritizes sensory signals arriving from the environment and could contribute to better understanding of disruptions in sensory perception observed in many neurological disorders.
