Gaze-Stabilizing Central Vestibular Neurons Project Asymmetrically to Extraocular Motoneuron Pools

Abstract

Within reflex circuits, specific anatomical projections allow central neurons to relay sensations to effectors that generate 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 rhombomeres 5–7 of 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 rotate their eyes following either nose-up or nose-down body tilts. This asymmetrically projecting central population thus participates in both upward 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 ethologically relevant 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 loss of these interneurons impairs a vital behavior, swim bladder inflation, 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.

Cellular resolution imaging of vestibular processing across the larval zebrafish brain

“…A third category, the commissural tangential neurons, innervate the contralateral octavolateral neuropil, perhaps permitting bilateral integration of vestibular signals from the two ears[33]. At the motor level, Thiele et al [38] have identified the nMLF as sufficient for driving tail deflections like the ones that we see in response to fictive vestibular stimuli (Fig 1 and ref [11]), and Schoppik et al[39] have identified vestibular neurons in rhombomeres 5-7 that control gaze stabilization.…”

Zebrafish Dscaml1 is Essential for Retinal Patterning and Function of Oculomotor Subcircuits

“…In response to nose-up pitch tilts, larvae will use their superior oblique and inferior rectus muscles to counter-rotate the eyes. Similarly, following nose-down pitch tilts, larvae stabilize their gaze using the superior rectus and inferior oblique muscles 38 . As expected, wild-type larvae at 5dpf showed strong VOR in response to 15° steps up or down away from horizontal, with a slightly stronger response to nose-up tilts.…”

“…Torsional eye movements were measured in 5 days post-fertilization fish in response to step tilts delivered using an apparatus similar in design to Schoppik et al . 2017 38 . All experiments took place in the dark.…”

A primal role for balance in the development of coordinated locomotion

“…The utricles transduce body orientation and self-motion but are insensitive to vertical forces orthogonal to the utricular macula [57, 58], and should therefore be irrelevant for execution or perception of lift forces directly. A central origin for the signals that guide coordination is therefore more plausible, Specifically in the utriclerecipient hindbrain vestibular nuclei [27, 59]. One of these, the tangential nucleus, contains “Ascending-Descending” neurons [60].…”