Glutamatergic Neurons in caudal Pontine Reticular Nucleus (PRNc) Mediate Backward Locomotion in mice

Abstract

Locomotion is essential for animals to adaptively navigate their environment. However, despite extensive investigation into neural mechanisms underlying forward movement, the brain circuits controlling backward locomotion, a critical motor behavior for navigating confined spaces and avoiding threats, remain poorly understood. Here, using a specially designed behavioral paradigm for backward locomotion in mice, we find that glutamatergic neurons in the caudal pontine reticular nucleus (PRNc) are selectively activated during backward, but not forward, locomotion. Activity increase of these neurons is temporally aligned with backward movement, with its amplitude correlated with speed. Optogenetic manipulations further demonstrate that these neurons are both sufficient and necessary for initiating and sustaining backward walking. Moreover, anatomical tracing reveals that the PRNc broadly integrates bilateral cortical and subcortical inputs and projects extensively to brain-wide and spinal cord networks. These findings suggest PRNc as a previously unrecognized brainstem center in direction-specific locomotor control circuits. Key findings of this work and our initial identification of this brainstem locomotor node were presented at the Society for Neuroscience Annual Meeting in November, 15th, 2025 (SfN Neuroscience 2025, San Diego, CA; Program No. PSTR027.02).