title: A novel form of presynaptic plasticity based on the fast reactivation of release sites switched off during low-frequency depression.
abstract: Repetitive firing of neurons at a low frequency often leads to a decrease in synaptic strength. The mechanism of this low-frequency depression (LFD) is poorly understood. Here, LFD was studied at Aplysia cholinergic synapses. The absence of a significant change in the paired-pulse ratio during LFD, together with the facts that neither the time course nor the extent of LFD were affected by the initial release probability, suggests that LFD is not related to a depletion of the ready-to-fuse synaptic vesicles (SVs) or to a decrease in the release probability, but results from the silencing of a subpopulation of release sites. A subset of SVs or release sites, which acquired a high release probability status during LFD, permits synapses to rapidly and temporarily recover the initial synaptic strength when the stimulation is stopped. However, the recovery of the full capacity of the synapse to sustain repetitive stimulations is slow and involves spontaneous reactivation of the silent release sites. Application of tetanic stimulations accelerates this recovery by immediately switching on the silent sites. This high-frequency-dependent phenomenon underlies a new form of synaptic plasticity that allows resetting of presynaptic efficiency independently of the recent history of the synapse. Microinjection of a mutated Aplysia synapsin that cannot be phosphorylated by cAMP-dependent protein kinase (PKA), or a PKA inhibitor both prevented high-frequency-dependent awakening of release sites. Changes in the firing pattern of neurons appear to be able to regulate the on-off status of release sites via a molecular cascade involving PKA-dependent phosphorylation of synapsin.
authors.affiliation: Centre National de la Recherche Scientifique and Université de Strasbourg, Institut des Neurosciences Cellulaires et Intégratives, Unité Propre de Recherche 3212, 67084 Strasbourg, France. doussau@inci-cnrs.unistra.fr
authors.forename: Frédéric
authors.initials: F
authors.lastname: Doussau
authors.forename: Yann
authors.initials: Y
authors.lastname: Humeau
authors.forename: Fabio
authors.initials: F
authors.lastname: Benfenati
authors.forename: Bernard
authors.initials: B
authors.lastname: Poulain
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D001048:Aplysia; D055592:Biophysical Phenomena / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017952:Ganglia, Invertebrate / Q000166:cytology; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D008274:Magnesium / Q000378:metabolism; D008845:Microinjections / Q000379:methods; D008959:Models, Neurological; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000166:cytology*; D018377:Neurotransmitter Agents / Q000378:metabolism; D011336:Probability; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
chemical_list: D004791:Enzyme Inhibitors; D018377:Neurotransmitter Agents; D008274:Magnesium; D002118:Calcium