The contribution of the mammalian visual cortex to stabilizing locomotion - PROJECT SUMMARY The mammalian visual cortex is most often thought of, and studied, in the context of its image-forming ability, enabling detection and identiflcation of objects in the environment. Much less is known, however, about the cortical contribution to non-image forming visual pathways. A critical function of these pathways is to use visual feedback to guide motor actions. The pathology of non-image forming pathways is especially severe, as even the basic capability to maintain heading during locomotion depends on vision. The goal of this project is to elucidate the cortical neural mechanisms that stabilize locomotion using visual feedback. Locomotion and balance become even more dependent on vision during aging, as the vestibular system declines. As a result, locomotion becomes progressively restricted in the elderly population, leading to poor physical and mental health. Therefore, the signiflcance of understanding the cortical visual pathways that stabilize locomotion and their plastic capacity to compensate for sensory loss, is paramount. In the mentored phase of the award, I will determine the neural circuitry for using visual feedback to stabilize locomotion in mice. I have developed a novel paradigm to evoke course-corrective turns in freely locomoting mice using closed-loop manipulations of visual feedback. Using this paradigm I have found that the mouse primary visual cortex plays a key role in course-correcting locomotion, and I will test the hypothesis that it does so by acting on the superior colliculus through subthalamic feed-forward inhibition. Supported by my excellent mentor and collaborators, I will combine intersectional viral approaches, optogenetics and large-scale electrophysiology and imaging techniques to achieve this goal. In the independent phase of the award, I will address the capacity for the visual cortex to modulate the subthalamic circuits that stabilize locomotion to compensate for sensory loss. I will flrst test the hypothesis that real time changes in subthalamic activity, guided by visual cortex, can determine the effect of visual feedback on locomotion. Finally, I will perform vestibular lesions to determine how the visual cortex compensates by changing subthalamic dynamics. I am confldent that this work will shed new light on the ability of the visual cortex to provide Ʋexible control over innate behavior. The technical and scientiflc expertise that I will acquire during the training period of the award will be crucial for setting the basis of my independent research program. In addition to this intense career development training, the guidance from my mentoring team, as well as the collaboration and the rich intellectual interaction in the UCSF neuroscience community will ensure my successful transition into an independent investigator, focusing on the contribution of the mammalian cortex to innate and learned behavior.
