Bassoon-disruption slows vesicle replenishment and induces homeostatic plasticity at a CNS synapse

• Published in: The EMBO journal 2014-03, Vol.33 (5), p.512-527
• Main Authors: Mendoza Schulz, Alejandro, Jing, Zhizi, María Sánchez Caro, Juan, Wetzel, Friederike, Dresbach, Thomas, Strenzke, Nicola, Wichmann, Carolin, Moser, Tobias
• Format: Article
• Language: English
• Subjects: active zone; Animals; Anterior Thalamic Nuclei - physiology; Anterior Thalamic Nuclei - ultrastructure; bassoon; Cellular biology; EMBO20; EMBO27; endbulb of Held; Fibers; homeostatic plasticity; Mice; Mice, Knockout; Mutation; Nerve Tissue Proteins - deficiency; Neurology; Neurons - physiology; Neurons - ultrastructure; Plasticity; Rodents; Synapses - physiology; Synapses - ultrastructure; Synaptic Vesicles - metabolism; vesicle replenishment
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1002/embj.201385887

Endbulb of Held terminals of auditory nerve fibers (ANF) transmit auditory information at hundreds per second to bushy cells (BCs) in the anteroventral cochlear nucleus (AVCN). Here, we studied the structure and function of endbulb synapses in mice that lack the presynaptic scaffold bassoon and exhibit reduced ANF input into the AVCN. Endbulb terminals and active zones were normal in number and vesicle complement. Postsynaptic densities, quantal size and vesicular release probability were increased while vesicle replenishment and the standing pool of readily releasable vesicles were reduced. These opposing effects canceled each other out for the first evoked EPSC, which showed unaltered amplitude. We propose that ANF activity deprivation drives homeostatic plasticity in the AVCN involving synaptic upscaling and increased intrinsic BC excitability. In vivo recordings from individual mutant BCs demonstrated a slightly improved response at sound onset compared to ANF, likely reflecting the combined effects of ANF convergence and homeostatic plasticity. Further, we conclude that bassoon promotes vesicular replenishment and, consequently, a large standing pool of readily releasable synaptic vesicles at the endbulb synapse. Synopsis This study integrates several approaches to reveal changes in structure and function of auditory endbulb synapses in the anteroventral cochlear nucleus (AVCN) of bassoon mouse mutants, that reflect direct effects of bassoon disruption at this synapse and homeostatic changes due to reduced input from the cochlea. Endbulb synapses upregulate presynaptic piccolo protein and postsynaptic densities. Unaltered synaptic transmission for first stimulus despite reduced size of the standing pool of readily releasable vesicles due to increased release probability and quantal size. Bassoon promotes vesicular replenishment and, consequently, a large standing pool of readily releasable synaptic vesicles. Sensory deprivation elicits homeostatic plasticity in the AVCN involving upscaling of the endbulb synapse and increased intrinsic BC excitability. Graphical Abstract The presynaptic scaffold protein Bassoon promotes synaptic vesicular replenishment and a large standing pool of readily releasable synaptic vesicles at synapses in the mouse auditory system.