Use-dependent decline of paired-pulse facilitation at Aplysia sensory neuron synapses suggests a distinct vesicle pool or release mechanism.
We have characterized paired-pulse facilitation at Aplysia sensory neuron-to-motoneuron synapses. This simple form of very short-term synaptic plasticity displayed an unusual feature: it decreased dramatically with repeated testing. Synaptic depression at these synapses and this use-dependent decrease in paired-pulse facilitation occurred independently of each other. Paired-pulse facilitation was inversely correlated with the size of the initial synaptic connection and was absent at stronger synapses. The use-dependent decrease in paired-pulse facilitation occurred at the same rate at large synapses as at small synapses, although the initial paired-pulse facilitation at large synapses was substantially smaller. Rates of synaptic depression were also independent of initial synaptic strength. Paired-pulse facilitation was blocked by presynaptic EGTA injection, but not by postsynaptic EGTA or BAPTA injection. These results indicate that presynaptic Ca2+ influx plays a critical role in paired-pulse facilitation. However, the persistence of the decrease in paired-pulse facilitation for longer than 15 min suggests that Ca2+ from the first paired action potential produces facilitation via a modulatory mechanism rather than by summating with Ca2+ influx during the second paired action potential in activating the Ca2+ binding sites that initiate exocytosis. This modulatory mechanism may not involve protein phosphorylation because paired-pulse facilitation was unaffected by the protein kinase inhibitors H7 and KN-62. These findings further suggest that release by the second paired action potential occurs at sites distinct from those that mediate release by the first action potential.
Jiang
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Departments of Pharmacology and Anesthesiology, University of Maryland School of Medicine, Baltimore, Maryland 21201-1559, USA.
Abrams
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D000200:Action Potentials; D000818:Animals; D001048:Aplysia / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D017952:Ganglia, Invertebrate / Q000502:physiology; D066298:In Vitro Techniques; D009046:Motor Neurons / Q000502:physiology; D009473:Neuronal Plasticity; D009475:Neurons, Afferent / Q000502:physiology*; D010766:Phosphorylation; D012701:Serotonin / Q000494:pharmacology; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects; D013572:Synaptic Vesicles / Q000378:metabolism / Q000502:physiology*
D012701:Serotonin; D004533:Egtazic Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium