Developmental regulation of the intracellular Ca2+ sensitivity of vesicle fusion and Ca2+-secretion coupling at the rat calyx of Held.
Developmental refinement of synaptic transmission can occur via changes in several pre- and postsynaptic factors, but it has been unknown whether the intrinsic Ca2+ sensitivity of vesicle fusion in the nerve terminal can be regulated during development. Using the calyx of Held, a giant synapse in the auditory pathway, we studied the presynaptic mechanisms underlying the developmental regulation of Ca2+-secretion coupling, comparing a time period before, and shortly after the onset of hearing in rats. We found an approximately 2-fold leftward shift in the relationship between EPSC amplitude and presynaptic Ca2+ current charge (QCa), indicating that brief presynaptic Ca2+ currents become significantly more efficient in driving release. Using a Ca2+ tail current protocol, we also found that the high cooperativity between EPSC amplitude and QCa was slightly reduced with development. In contrast, in presynaptic Ca2+ uncaging experiments, the intrinsic Ca2+ cooperativity of vesicle fusion was identical, and the intrinsic Ca2+ sensitivity was slightly reduced with development. This indicates that the significantly enhanced release efficiency of brief Ca2+ currents must be caused by a tighter co-localization of Ca2+ channels and readily releasable vesicles, but not by changes in the intrinsic properties of Ca2+-dependent release. Using the parameters of the intrinsic Ca2+ sensitivity measured at each developmental stage, we estimate that during a presynaptic action potential (AP), a given readily releasable vesicle experiences an about 1.3-fold higher 'local' intracellular Ca2+ concentration ([Ca2+]i) signal with development. Thus, the data indicate a tightening in the Ca2+ channel-vesicle co-localization during development, without a major change in the intrinsic Ca2+ sensitivity of vesicle fusion.
Kochubey
Olexiy
O
Laboratory of Synaptic Mechanisms, Brain-Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
Han
Yunyun
Y
Schneggenburger
Ralf
R
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000375:Aging / Q000502:physiology; D000818:Animals; D001306:Auditory Pathways / Q000254:growth & development / Q000502:physiology*; D001933:Brain Stem / Q000254:growth & development / Q000502:physiology*; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000502:physiology; D020013:Calcium Signaling / Q000502:physiology*; D003627:Data Interpretation, Statistical; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D018377:Neurotransmitter Agents / Q000378:metabolism / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D013572:Synaptic Vesicles / Q000502:physiology*
D015220:Calcium Channels; D018377:Neurotransmitter Agents; D002118:Calcium