Development of vestibular behaviors in zebrafish

Abstract

Most animals orient their bodies with respect to gravity to facilitate locomotion and perception. The neural circuits responsible for these orienting movements have long served as a model to address fundamental questions in systems neuroscience. Though postural control is vital, we know little about development of either balance reflexes or the neural circuitry that produces them. Recent work in a genetically and optically accessible vertebrate, the larval zebrafish, has begun to reveal the mechanisms by which such vestibular behaviors and circuits come to function. Here we highlight recent work that leverages the particular advantages of the larval zebrafish to illuminate mechanisms of postural development, the role of sensation for balance circuit development, and the organization of developing vestibular circuits. Further, we frame open questions regarding the developmental mechanisms for functional circuit assembly and maturation where studying the zebrafish vestibular system is likely to open new frontiers.

Figure 1. A diagram of forces that stabilize and destabilize larval zebrafish posture

A) Three axes of rotation: Roll, Pitch (nose-up/nose-down) and Yaw (left/right turns). B) Forces in the pitch axis: the buoyant force acts at the center of volume (green circle) to elevate the fish; gravity acts at the center of mass (magenta circle) to pull the fish down. The center of mass sits forward of the center of gravity which leads to a nose-down torque that will rotate a passive fish nose-down. C) During forward translation, or in flow, the fish will rotate (shown here in the pitch axis) to align with the direction of drag (blue lines). The center of pressure (blue circle) is displaced caudally to the center of mass (pink circle) about which the fish rotates. This displacement acts as a moment arm, schematized in the corner, that generates stabilizing torque (black arrow) to align the body.

Figure 2. Schematic of vestibular circuits subserving posture and gaze stabilization

A) At the onset of movement, the utricular otolith slides relative to the hair cells underneath, depolarizing some (black) and hyperpolarizing others (gray), depending on their ciliary orientation. Vestibular afferents (blue) relay hair cell signals to vestibulospinal neurons in the hindbrain (green). This vestibular drive sets up asymmetric activation of trunk musculature through as-yet unclear connectivity that is thought to rely both on direct synapses with motor neurons as well as indirectly via spinal premotor populations (Kasumacic et al., 2015; Murray et al., 2018). In this example, as the fish rolls to the left, stronger motor drive to ventral muscle on the right and dorsal muscle on the left (gray shaded regions) produces a self-righting torque (Bagnall and McLean, 2014). B) Equivalent schematic for vestibular-driven gaze stabilization. Here the brainstem vestibular nuclei are known to make direct connections to oculomotor neurons. Recent work has revealed that in pitch-related circuits, vestibulo-ocular neurons driving eye rotation downwards (active pathway, dark green) outnumber those driving upwards eye movements (inhibited pathway, pale green) by 6:1 (Schoppik et al., 2017).