title: Action potential bursts enhance transmitter release at a giant central synapse.
abstract: Patterns of action potentials (APs), often in the form of bursts, are critical for coding and processing information in the brain. However, how AP bursts modulate secretion at synapses remains elusive. Here, using the calyx of Held synapse as a model we compared synaptic release evoked by AP patterns with a different number of bursts while the total number of APs and frequency were fixed. The ratio of total release produced by multiple bursts to that by a single burst was defined as 'burst-effect'.We found that four bursts of 25 stimuli at 100 Hz increased the totalcharge of EPSCs to 1.47 ± 0.04 times that by a single burst of 100 stimuli at the same frequency.Blocking AMPA receptor desensitization and saturation did not alter the burst-effect, indicating that it was mainly determined by presynaptic mechanisms. Simultaneous dual recordings of presynaptic membrane capacitance (Cm) and EPSCs revealed a similar burst-effect, being 1.58±0.13by Cm and 1.49±0.05 by EPSCs. Reducing presynapticCa2+ influx by lowering extracellular Ca2+concentration or buffering residual intracellular Ca2+ with EGTA inhibited the burst-effect. We further developed a computational model largely recapitulating the burst-effect and demonstrated that this effect is highly sensitive to dynamic change in availability of the releasable pool of synaptic vesicles during various patterns of activities. Taken together, we conclude that AP bursts modulate synaptic output mainly through intricate interaction between depletion and replenishment of the large releasable pool. This burst-effect differs from the somatic burst-effect previously described from adrenal chromaffin cells, which substantially depends on activity-induced accumulation of Ca2+ to facilitate release of a limited number of vesicles in the releasable pool. Hence, AP bursts may play an important role in dynamically regulating synaptic strength and fidelity during intense neuronal activity at central synapses.
authors.affiliation: Institute of Molecular Medicine, Peking University, Beijing 100871, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Liang
authors.initials: L
authors.lastname: Sun
authors.forename: Yi-Mei
authors.initials: YM
authors.lastname: Yang
authors.forename: Hong-Ping
authors.initials: HP
authors.lastname: Huang
authors.forename: Fei-Peng
authors.initials: FP
authors.lastname: Zhu
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Zhang
authors.forename: Shu
authors.initials: S
authors.lastname: Guo
authors.forename: Pan-Li
authors.initials: PL
authors.lastname: Zuo
authors.forename: Claire X
authors.initials: CX
authors.lastname: Zhang
authors.forename: Jiu-Ping
authors.initials: JP
authors.lastname: Ding
authors.forename: Lu-Yang
authors.initials: LY
authors.lastname: Wang
authors.forename: Zhuan
authors.initials: Z
authors.lastname: Zhou
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001933:Brain Stem / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D003198:Computer Simulation; D025802:Electric Capacitance; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005089:Exocytosis / Q000187:drug effects; D066298:In Vitro Techniques; D051379:Mice; D008959:Models, Neurological; D018377:Neurotransmitter Agents / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors
chemical_list: D002614:Chelating Agents; D018377:Neurotransmitter Agents; D002118:Calcium