RT Journal Article SR Electronic T1 Gaze-stabilizing central vestibular neurons project asymmetrically to extraocular motoneuron pools JF bioRxiv FD Cold Spring Harbor Laboratory SP 151548 DO 10.1101/151548 A1 David Schoppik A1 Isaac H. Bianco A1 David A. Prober A1 Adam D. Douglass A1 Drew N. Robson A1 Jennifer M.B. Li A1 Joel S.F. Greenwood A1 Edward Soucy A1 Florian Engert A1 Alexander F. Schier YR 2017 UL http://biorxiv.org/content/early/2017/06/18/151548.abstract AB Within reflex circuits, specific anatomical projections allow central neurons to relay sensations to effectors that generate compensatory movements. A major challenge is to relate anatomical features of central neural populations — such as asymmetric connectivity — to the computations the populations perform. To address this problem, we mapped the anatomy, modeled the function, and discovered a new behavioral role for a genetically-defined population of central vestibular neurons in larval zebrafish. First, we found that neurons within this central population project preferentially to motoneurons that move the eyes downward. Concordantly, when the entire population of asymmetrically-projecting neurons was stimulated collectively, only downward eye rotations were observed, demonstrating a functional correlate of the anatomical bias. When these neurons are ablated, fish failed to display the eye rotations normally observed following nose-up or nose-down body tilts. This asymmetrically-projecting central population thus participates in both up and downward gaze stabilization. In addition to projecting to motoneurons, central vestibular neurons also receive direct sensory input from peripheral afferents. To infer whether asymmetric projections can facilitate sensory encoding or motor output, we modeled differentially-projecting sets of central vestibular neurons. Whereas motor command strength was independent of projection allocation, asymmetric projections enabled more accurate representation of nose-up stimuli. The model shows how asymmetric connectivity could enhance the representation of imbalance during nose-up postures while preserving gaze-stabilization performance. Finally, we found that central vestibular neurons were necessary for a vital behavior requiring maintenance of a nose-up posture: swim bladder inflation. These observations suggest that asymmetric connectivity in the vestibular system facilitates representation of ethologicallyrelevant stimuli without compromising reflexive behavior.Significance Statement Interneuron populations use specific anatomical projections to transform sensations into reflexive actions. Here we examined how the anatomical composition of a genetically-defined population of balance interneurons in the larval zebrafish relates to the computations it performs. First, we found that the population of interneurons that stabilize gaze preferentially project to motoneurons that move the eyes downward. Next, we discovered through modeling that such projection patterns can enhance the encoding of nose-up sensations without compromising gaze stabilization. Finally we found that these interneurons are also responsible for a vital behavior that relies on maintaining a nose-up posture. These observations suggest that anatomical specialization permits neural circuits to represent relevant features of the environment without compromising behavior.