A Generalized Spatial Progress Code for Navigation in the Medial Prefrontal Cortex

Abstract

Goal-directed navigation requires an internal estimate of progress toward a desired outcome, yet how the brain constructs and represents such a signal remains unclear. Here, we designed a multi-route navigation paradigm with geometrically distinct paths and imaged medial prefrontal cortex (mPFC) activity as mice performed goal-directed route choice behavior. We found that a substantial fraction of mPFC neurons fired at consistent positions along a normalized start-to-goal axis, independent of path geometry, running direction, and task context. At the ensemble level, mPFC activity reliably decoded spatial progress but carried minimal information about path identity. This progress code emerged with task familiarity and required input from the hippocampal CA1. Inactivation of either mPFC or CA1[->]mPFC projection did not disrupt learned path preference but impaired navigational fluency in trained mice. These findings reveal a hippocampal-prefrontal mechanism for representing abstract, context-generalized spatial progress within a goal-directed navigational episode, supporting fluent navigation across variable routes.