Piccolo Promotes Vesicle Replenishment at a Fast Central Auditory Synapse

Area of Science:

• Neuroscience
• Molecular Biology
• Synaptic Physiology

Background:

• Piccolo and Bassoon are key cytomatrix active zone (CAZ) proteins essential for neurotransmitter release.
• Their functional redundancy has been debated, necessitating studies to segregate their roles.

Purpose of the Study:

• To elucidate the distinct roles of Piccolo and Bassoon in regulating synaptic transmission at central auditory synapses.
• To investigate the impact of Piccolo deficiency and combined Piccolo-Bassoon deficiency on synaptic vesicle dynamics.

Main Methods:

• Genetic manipulation to create Piccolo-deficient and double-mutant (Piccolo/Bassoon) mice.
• Semi-quantitative immunohistochemistry, electron microscopy, and in vitro/in vivo electrophysiology.
• Analysis of synaptic transmission, vesicle pools, and protein localization at endbulb of Held synapses.

Main Results:

• Piccolo deficiency reduced readily releasable pool (RRP) size and impaired synaptic vesicle (SV) replenishment, slowing recovery from depression.
• Piccolo deficiency increased Bassoon abundance at active zones (AZs) and reduced RIM1.
• Double-mutant synapses showed increased release probability and exacerbated SV replenishment deficits.

Conclusions:

• Piccolo and Bassoon play additive roles in SV replenishment, influencing RRP size and organization.
• Bassoon has an additional role in regulating neurotransmitter release probability.
• These findings clarify the distinct contributions of Piccolo and Bassoon to synaptic function.