Temporal Vestibular Deficits in synaptojanin 1 (synj1) Mutants

Abstract

The lipid phosphatase synaptojanin 1 (synj1) is required for the disassembly of clathrin coats on endocytic compartments. In neurons such activity is necessary for the recycling of endocytosed membrane into synaptic vesicles. Mutations in zebrafish synj1 have been shown to disrupt the activity of ribbon synapses in sensory hair cells. After prolonged mechanical stimulation of hair cells, both phase locking of afferent nerve activity and the recovery of spontaneous release of synaptic vesicles are diminished in synj1 mutants. Presumably as a behavioral consequence of these synaptic deficits, synj1 mutants are unable to maintain an upright posture. To probe vestibular function with respect to postural control in synj1 mutants, we developed a method for assessing the vestibulospinal reflex (VSR) in larvae. We elicited the VSR by rotating the head and recorded tail movements. As expected, the VSR is completely absent in pcdh15a and lhfpl5a mutants that lack inner ear function. Conversely, lhfpl5b mutants, which have a selective loss of function of the lateral line organ, have normal VSRs, suggesting that the hair cells of this organ do not contribute to this reflex. In contrast to mechanotransduction mutants, the synj1 mutant produces normal tail movements during the initial cycles of rotation of the head. Both the amplitude and temporal aspects of the response are unchanged. However, after several rotations, the VSR in synj1 mutants was strongly diminished or absent. Mutant synj1 larvae are able to recover, but the time required for the reappearance of the VSR after prolonged stimulation is dramatically increased in synj1 mutants. Collectively, the data demonstrate a behavioral correlate of the synaptic defects caused by the loss of synj1 function. Our results suggest that defects in synaptic vesicle recycling give rise to fatigue of ribbons synapses and possibly other synapses of the VS circuit, leading to the loss of postural control.

The organization of the gravity-sensing system in zebrafish

“…Acoustic stimuli can trigger Mauthner-mediated escape behaviors 40 , but to date utricular stimuli have been shown to elicit locomotion, not escape 41,42 . We reasoned that the utricular afferents exciting the Mauthner cell are striolar-driven (Fig.…”

“…Therefore, these commissural escape neurons are presumably similarly tuned to inertial movements as the contralateral Mauthner cell that they contact. Vestibular stimuli can elicit locomotion 27,28 , but escape behaviors have primarily been evoked with auditory or mixed auditory-vestibular stimuli that do not allow isolation of the vestibular component 29,30 . We reasoned that the utricular afferents exciting the Mauthner cell are tuned to report ipsilateral head tilts and therefore contralateral translational movements, with the predicted consequence that a translational movement to the left should trigger escape bends to the left (Fig.…”

Organization of the gravity-sensing system in zebrafish

“…Vestibular stimuli can elicit locomotion 28,29 , but escape behaviors have primarily been evoked with auditory or mixed auditory-vestibular stimuli that do not allow isolation of the vestibular component 30,31 . We reasoned that the utricular afferents exciting the Mauthner cell are tuned to report ipsilateral head tilts and therefore contralateral translational movements, with the predicted consequence that a translational movement to the left should trigger escape bends to the left (Fig.…”

Defects in exosome biogenesis are associated with sensorimotor defects in zebrafishvps4amutants

“…As mutant larvae have pronounced postural defects, we also tested the vestibulospinal reflex (VSR), which assesses vestibular induced motor function in the trunk (Gao and Nicolson, 2021). We compared the maximum tail angle between wild-type siblings and mutants and found the vps4a T248I mutants had a significantly reduced tail angle ( p = 0.0012 (exact), nWT = 7, n vps4a(T248I) = 10, Mann-Whitney test) (Fig.…”

“…As mutant larvae have pronounced postural defects, we also tested the vestibulospinal reflex (VSR), which assesses vestibular induced motor function in the trunk (Gao and Nicolson, 2021).…”