SSFO-mediated optogenetic activation of the mouse superior colliculus results in a repeatable behavioral response

Abstract

The superior colliculus (SC) is a conserved midbrain structure responsible for reflexive behavioral responses to external stimuli, such as escaping predators and pursuing objects of interest. Unilateral electrical stimulation of the SC has been shown to elicit ipsilateral (escaping) and contralateral (pursuing) movements. To further investigate the response properties of these circuits, we revisited these experiments using an optogenetic approach. In particular, we used the stabilized step function opsin SSFO (ChR2 C128S/D156A), which has slow channel kinetics, allowing it to remain in an open state for 20 – 30 minutes. As such, a short pulse of blue light results in prolonged depolarization of SSFO-expressing cells. SSFO was introduced via viral vector injection in the right SC of C57Bl6J mice, incorporating it in neurons of both the superficial and deeper layers of the SC. Provided with blue light stimulation, mice repeatedly showed a strong behavioral response. At first, they ran around in their cage for 20 – 30 seconds as if escaping from a non-existing threat. After quieting down, mice displayed characteristic movements consisting of large counterclockwise body turns, which became shorter and less frequent as time progressed. Nevertheless, a preference for counterclockwise turning was detectable up to 30 minutes after stimulation of the right SC. Notably, repeating these stimulations yielded a similar result, indicating a reproducible activation. In summary, SSFO-mediated optogenetic stimulation can directly elicit a complex and prolonged behavioral response, including escape- and pursuit-like movements, corresponding to what has been observed upon electric stimulation. Moreover, the timing of this behavioral response closely mimics the duration of the SSFO ‘open state’ conformation. Taken together, we demonstrated the potential of optogenetics to repeatedly activate the natural functions of neuronal circuits for a prolonged period of time. Future experiments will investigate the effect of SC layer- and cell type-specific stimulation to further elucidate the way orienting behavior is governed.status: publishe