title: Superpriming of synaptic vesicles as a common basis for intersynapse variability and modulation of synaptic strength.
abstract: Glutamatergic synapses show large variations in strength and short-term plasticity (STP). We show here that synapses displaying an increased strength either after posttetanic potentiation (PTP) or through activation of the phospholipase-C-diacylglycerol pathway share characteristic properties with intrinsically strong synapses, such as (i) pronounced short-term depression (STD) during high-frequency stimulation; (ii) a conversion of that STD into a sequence of facilitation followed by STD after a few conditioning stimuli at low frequency; (iii) an equalizing effect of such conditioning stimulation, which reduces differences among synapses and abolishes potentiation; and (iv) a requirement of long periods of rest for reconstitution of the original STP pattern. These phenomena are quantitatively described by assuming that a small fraction of "superprimed" synaptic vesicles are in a state of elevated release probability (p ∼ 0.5). This fraction is variable in size among synapses (typically about 30%), but increases after application of phorbol ester or during PTP. The majority of vesicles, released during repetitive stimulation, have low release probability (p ∼ 0.1), are relatively uniform in number across synapses, and are rapidly recruited. In contrast, superprimed vesicles need several seconds to be regenerated. They mediate enhanced synaptic strength at the onset of burst-like activity, the impact of which is subject to modulation by slow modulatory transmitter systems.
authors.affiliation: Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany; Center for Nanoscale Microscopy and Molecular Physiology of the Brain, 37073 Göttingen, Germany;
authors.forename: Holger
authors.initials: H
authors.lastname: Taschenberger
authors.affiliation: Center for Nanoscale Microscopy and Molecular Physiology of the Brain, 37073 Göttingen, Germany; Emeritus Group Membrane Biophysics, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany.
authors.forename: Andrew
authors.initials: A
authors.lastname: Woehler
authors.affiliation: Center for Nanoscale Microscopy and Molecular Physiology of the Brain, 37073 Göttingen, Germany; Emeritus Group Membrane Biophysics, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany eneher@gwdg.de.
authors.forename: Erwin
authors.initials: E
authors.lastname: Neher
mesh_terms: D000465:Algorithms; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D008959:Models, Neurological; D009473:Neuronal Plasticity / Q000502:physiology; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology; D013569:Synapses / Q000378:metabolism / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D013572:Synaptic Vesicles / Q000378:metabolism / Q000502:physiology*
chemical_list: D018698:Glutamic Acid
keywords: Munc13; calyx of Held; phorbol ester; posttetanic potentiation; short-term plasticity