Directional Reaching for Water as a Cortex-Dependent Behavioral Framework for Mice

Optogenetic tools and imaging methods for recording and manipulating brain activity have boosted the field of neuroscience in unprecedented ways. However, behavioral paradigms for mice lag behind those of primates, limiting the full potential of such tools. Here, we present an innovative behavioral framework in which head-fixed mice directionally reach for water droplets, similar to the primate “center-out” reaching task. Mice rapidly engaged in the task, performed hundreds of trials, and reached in multiple directions when droplets were presented at different locations. Surprisingly, mice used chemosensation to determine the presence of water droplets. Optogenetic inactivation of the motor cortex halted the initiation and rapidly diverted the trajectory of ongoing movements. Layer 2/3 two-photon imaging revealed robust direction selectivity in most reach-related neurons. Finally, mice performed directional reaching instructed by vibratotactile stimuli, demonstrating the potential of this framework for studying, in addition to motor control, sensory processing, and decision making. [Display omitted] •Mice rapidly learn to reach for water droplets in multiple directions using chemosensation•Directional reaching can be instructed by arbitrary sensorimotor associations•Optogenetic motor cortex silencing halts movement initiation and ongoing reaching•Motor cortex layer 2/3 neurons display a high degree of directional selectivity Galiñanes et al. present a behavioral framework for systems neuroscience in which mice learn to reach for water droplets presented at multiple locations, similar to the primate center-out task. Reaching is guided by chemosensory cues and depends on motor cortex. Layer 2/3 neurons display a high degree of directional selectivity.