Mild and Reversible Proprioception Perturbation Suggests Causal Biomechanics for Memory-Dependent Spatial Behavior in Mice

Abstract

The neural system at the periphery is a frontline for embodied cognition, yet an acute, mild perturbation to dissect functional causality is hard to achieve. Peripheral neural processes and the central nervous system may work in concert to generate sophisticated representations regarding self and environments in the brain. This hypothesis, together with the underlying mechanisms, is particularly difficult to test for certain sensory inputs due to the lack of reversible manipulation techniques. Long postulated as a component for path integration, proprioception is one of such modalities. In this study, we developed a murine experimental system to manipulate proprioceptive inputs during memory-dependent localization task (which required precise operant-conditioned licks) in spatial virtual reality (VR). Through bioluminescent optogenetics (luminopsin) selectively expressed in the parvalbumin-positive neurons of the dorsal root ganglia in mice, proprioceptive processing was compromised directly from the periphery to bypass the bottleneck of specific central targeting, which results from the lack of anatomically or genetically dedicated proprioceptive circuits in the brain. In-vivo IVIS imaging and behavior suggested the effects of luminopsin last for roughly 20 minutes. While mice exhibited normal performance in tasks relying on gross motor skills, they showed subtle deficits in challenging spatial tasks that required integration of past movements. These observations support a task-specific role for proprioception, and demonstrate a potential of chemogenetics-like, rapidly reversible strategies for characterizing peripherally defined sensory contribution to spatial cognition. Future work will optimize this approach; for instance, to activate opsins by light with millisecond precision. To our knowledge, this is a first causal demonstration for acute participation of proprioception in path-integration biomechanics, enabling the first temporally defined method for mild perturbation of path-integration mechanisms.