title: Facilitation at single synapses probed with optical quantal analysis.
abstract: Many synapses can change their strength rapidly in a use-dependent manner, but the mechanisms of such short-term plasticity remain unknown. To understand these mechanisms, measurements of neurotransmitter release at single synapses are required. We probed transmitter release by imaging transient increases in [Ca(2+)] mediated by synaptic N-methyl-D-aspartate receptors (NMDARs) in individual dendritic spines of CA1 pyramidal neurons in rat brain slices, enabling quantal analysis at single synapses. We found that changes in release probability, produced by paired-pulse facilitation (PPF) or by manipulation of presynaptic adenosine receptors, were associated with changes in glutamate concentration in the synaptic cleft, indicating that single synapses can release a variable amount of glutamate per action potential. The relationship between release probability and response size is consistent with a binomial model of vesicle release with several (>5) independent release sites per active zone, suggesting that multivesicular release contributes to facilitation at these synapses.
authors.affiliation: Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Oertner
authors.forename: Bernardo L
authors.initials: BL
authors.lastname: Sabatini
authors.forename: Esther A
authors.initials: EA
authors.lastname: Nimchinsky
authors.forename: Karel
authors.initials: K
authors.lastname: Svoboda
mesh_terms: D015762:2-Chloroadenosine / Q000494:pharmacology; D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000032:analysis / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D009473:Neuronal Plasticity / Q000502:physiology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D012684:Sensory Thresholds / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
chemical_list: D018377:Neurotransmitter Agents; D016194:Receptors, N-Methyl-D-Aspartate; D018047:Receptors, Purinergic P1; D015762:2-Chloroadenosine; D018698:Glutamic Acid; D002118:Calcium