Central Vestibular Tuning Arises from Patterned Convergence of Otolith Afferents

Abstract

As sensory information moves through the brain, higher-order areas exhibit more complex tuning than lower areas. Though models predict this complexity is due to convergent inputs from neurons with diverse response properties, in most vertebrate systems convergence has only been inferred rather than tested directly. Here we measure sensory computations in zebrafish vestibular neurons across multiple axes in vivo. We establish that whole-cell physiological recordings reveal tuning of individual vestibular afferent inputs and their postsynaptic targets. An independent approach, serial section electron microscopy, supports the inferred connectivity. We find that afferents with similar or differing preferred directions converge on central vestibular neurons, conferring more simple or complex tuning, respectively. Our data also resolve a long-standing contradiction between anatomical and physiological analyses by revealing that sensory responses are produced by sparse but powerful inputs from vestibular afferents. Together these results provide a direct, quantifiable demonstration of feedforward input convergence in vivo.

Synaptic Encoding of Vestibular Sensation Regulates Movement Timing and Coordination

“…Distinct EPSC bins might reflect input from single VIII th nerve afferents with different stable resting amplitudes [46, 47] as proposed for comparable recordings done in the light [32]. To test if EPSCs within a distinct amplitude bin in our recordings derived from a single afferent neuron, we compared empirical within-bin refractory period violations to a model estimate of expected violations accounting for noisy bin assignations and within-bin event frequency (Figure S1).…”

“…al. examining how larval zebrafish vestibulospinal neurons acquire peripheral selectivity [32] by mapping the inhibitory synaptic inputs and defining the behavioral utility for vestibulospinal activity (Figure 8). Intriguingly, our characterization of excitatory inputs disagrees with theirs, suggesting a potential role for modulation of vestibulospinal inputs.…”

“…Recent work has used larval zebrafish to explore vertebrate vestibular circuits, but our understanding of neuronal development and synaptic architecture remains incomplete. In larval zebrafish, spinal-projecting hindbrain neurons [29–31] encode postural information from the utricle [32]. However vestibulospinal development remains poorly understood, making links to behavior tenuous.…”

Crossbill: an open access single objective light-sheet microscopy platform

“…Here, we image larval zebrafish samples expressing GFP in a subset of brain and spinal cord neurons to demonstrate this capability. Figure 2 and Supplementary Video 2 show the imaging at 5 days post fertilization (dpf) larvae of Tg[nefma:gal4;uas:gfp] zebrafish [21]. The dataset was acquired using the Crossbill software at 20 fps camera frame rate.…”

“…All procedures for zebrafish imaging conform to NIH guidelines on animal experimentation and were approved by the Northwestern University Institutional Animal Care and Use Committee. Experiments were performed using 5-day-old transgenic zebrafish larvae, Tg[nefma:gal4;uas:GFP] [21], when they have a fully inflated swim bladder and are free-swimming. Briefly, larvae were anesthetized in 0.02% w/v ethyl 3-aminobenzoate methanesulfonic acid (MS-222; Sigma Aldrich), transferred to a glass-bottomed dish, and embedded upright in low-melting-point agar (1.4% in system water).…”