A pre-cerebellar brainstem integrator implements self-location memory and enables positional homeostasis

To track and control self-location, animals integrate their movements through space. Representations of self-location are observed in the mammalian hippocampal formation (1,2), but it is unknown if positional representations exist in more ancient brain regions, how they arise from integrated self-motion, and by what pathways they control locomotion. Here, in a head-fixed, fictive-swimming, virtual-reality preparation (3), we exposed larval zebrafish to a variety of involuntary displacements. They tracked these displacements and, many seconds later, moved toward their earlier location through corrective swimming (‘positional homeostasis’). This behavior is captured by a control system that integrates visual motion into a displacement estimate and combines this with instantaneous velocity to drive corrective swimming. Based on this control theoretic description, we screened the entire brain at cellular resolution for neural activity representing self-location. Whole-brain functional imaging revealed a network in the medulla (SLO-MO for Self Location encoding Medulla Oblongata neurons) that stores a memory of location and induces an error signal in the inferior olive to drive future corrective swimming. Activity of SLO-MO neurons integrates visual motion into a persistent signal, with individual neurons persisting for a variety of timescales. Ablating one functional class of SLO-MO cells, such as those encoding forward displacements, abolishes the memory capacity of the other functional class (such as neurons encoding backward displacements), suggesting recurrent connectivity implementing attractor dynamics. Ablating SLO-MO also abolishes displacement-memory behavior. Optogenetically manipulating SLO-MO cells evokes displacement-memory behavior as if memories are optically ‘implanted’. SLO-MO connects to the inferior olive, where it induces a long-lasting displacement error signal that is communicated to the cerebellum. Consistent with this multiregional circuit diagram, ablating inferior olive cells abolishes displacement corrections. These results reveal a multiregional hindbrain circuit in vertebrates that integrates self-motion and stores self-location to control locomotor behavior.