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.

Grant Number: 1K99EY037782-01
NIH Institute/Center: NIH
Principal Investigator: Gal Atlan