Quantal analysis estimates docking site occupancy determining short‐term depression at hippocampal glutamatergic synapses. (13th November 2021)

• Record Type: Journal Article
• Authors: Tanaka, Mamoru; Sakaba, Takeshi; Miki, Takafumi
• Is Part Of: Journal of physiology. Volume 599:Number 23(2021)
• Page Start: 5301
• Page End: 5327
• Publication Date: 2021-11-13
• Subjects: glutamatergic synapse -- hippocampus -- neurotransmitter release -- release site -- synaptic depression; Physiology -- Periodicals; 612.005
• DOI: 10.1113/JP282235
• Languages: English
• ISSNs: 0022-3751

Abstract

Abstract : Abstract: Before fusion, synaptic vesicles (SVs) pause at discrete release/docking sites. During repetitive stimulation, the probability of site occupancy changes following SV fusion and replenishment. The occupancy probability is considered to be one of the crucial determinants of synaptic strength, but it is difficult to estimate separately because it usually blends with other synaptic parameters. Thus, the contribution of site occupancy to synaptic function, particularly to synaptic depression, remains elusive. Here, we directly estimated the occupancy probability at the hippocampal mossy fibre‐CA3 interneuron synapse showing synaptic depression, using statistics of counts of vesicular events detected by deconvolution. We found that this synapse had a particularly high occupancy (∼0.85) with a high release probability of a docked SV (∼0.8) under 3 mm external calcium conditions. Analyses of quantal amplitudes and SV counts indicated that quantal size reduction decreased the amplitudes of all responses in a train to a similar degree, whereas release/docking site number was unchanged during trains, suggesting that quantal size and release/docking site number had little influence on the extent of synaptic depression. Model simulations revealed that the initial occupancy with high release probability and slow replenishment determined the time course of synaptic depression. Consistently, decreasing external calcium concentration reduced both the occupancy and release probability, and the reductions in turn produced less depression. Based on these results, we suggest that the occupancy probability is a crucial determinant of short‐term synaptic depression at glutamatergic synapses in the hippocampus. Key points: The occupancy probability of a release/docking site by a synaptic vesicle at presynaptic terminals is considered to be one of the crucial determinants of synaptic strength, but it is difficult to estimate separately from other synaptic parameters. Here, we directly estimate the occupancy probability at the hippocampal mossy fibre‐interneuron synapse using statistics of vesicular events detected by deconvolution. We show that the synapses have particularly high occupancy (0.85) with high release probability (0.8) under high external calcium concentration ([Ca 2+ ]o ) conditions, and that both parameter values change with [Ca 2+ ]o, shaping synaptic depression. Analyses of the quantal amplitudes and synaptic vesicle counts suggest that quantal sizes and release/docking site number have little influence on the extent of synaptic depression. The results suggest that the occupancy probability is a crucial determinant of short‐term synaptic depression at glutamatergic synapses in the hippocampus. Abstract : Abstract figure legend In hippocampus, small en passant mossy fibre (hMF) synapses innervate interneurons of the CA3 stratum lucidum (SLIN) with a single active zone. The synapse displays depression under high release probability conditions. Analysis of counts of vesicular events detected by deconvolution demonstrates that the time course of EPSC depression matches that of the reduction in the number of released vesicles. The reduction in vesicle counts during a train of stimuli mainly results from that in the probability of vesicle occupancy at a docking site at the hMF‐SLIN synapses.