Temporal Vestibular Deficits in synaptojanin 1 (synj1) Mutants

Area of Science:

• Neuroscience
• Cell Biology
• Genetics

Background:

• Synaptojanin 1 (synj1) is a lipid phosphatase essential for clathrin coat disassembly during endocytosis.
• Efficient synaptic vesicle recycling is vital for neuronal function, particularly in sensory systems and maintaining posture.
• Mutations in synj1 in zebrafish disrupt ribbon synapse activity in sensory hair cells, leading to postural instability.

Purpose of the Study:

• To investigate the role of synj1 in vestibular function and postural control using a zebrafish model.
• To characterize the vestibulospinal reflex (VSR) in synj1 mutants after mechanical stimulation.
• To correlate synaptic vesicle recycling defects with behavioral deficits in synj1 mutants.

Main Methods:

• Developed a method to assess the vestibulospinal reflex (VSR) in larval zebrafish by head rotation and tail movement recording.
• Compared VSR in synj1 mutants with control and other inner ear/lateral line mutants (pcdh15a, lhfpl5a, lhfpl5b).
• Analyzed VSR amplitude, temporal aspects, and recovery time after prolonged stimulation.

Main Results:

• Synj1 mutants exhibited normal initial VSR but showed diminished or absent VSR after prolonged head rotation.
• The recovery time for VSR reappearance was significantly increased in synj1 mutants.
• Other inner ear mutants (pcdh15a, lhfpl5a) lacked VSR, while lateral line mutants (lhfpl5b) had normal VSR, confirming the VSR's reliance on inner ear function.

Conclusions:

• Loss of synj1 function leads to synaptic fatigue in ribbon synapses and potentially other vestibular circuit synapses.
• Defects in synaptic vesicle recycling are behaviorally manifested as impaired VSR and loss of postural control in synj1 mutants.
• Synj1 is critical for sustained synaptic function and maintaining balance in zebrafish.