Paired-Pulse Depression of Unitary Quantal Amplitude at Single Hippocampal Synapses

At central synapses, quantal size is generally regarded as fluctuating around a fixed mean with little change during short-term synaptic plasticity. We evoked quantal release by brief electric stimulation at single synapses visualized with FM 1-43 dye in hippocampal cultures. The majority of quantal...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 101; no. 4; pp. 1063 - 1068
Main Authors Chen, Gong, Harata, Nobutoshi C., Tsien, Richard W.
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 27.01.2004
National Acad Sciences
SeriesFrom the Cover
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Online AccessGet full text
ISSN0027-8424
1091-6490
DOI10.1073/pnas.0307149101

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Summary:At central synapses, quantal size is generally regarded as fluctuating around a fixed mean with little change during short-term synaptic plasticity. We evoked quantal release by brief electric stimulation at single synapses visualized with FM 1-43 dye in hippocampal cultures. The majority of quantal events evoked at single synapses were monovesicular, based on examination of amplitude distribution of a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-receptor-mediated responses. Consistent with previous findings, the quantal size did not change during paired-pulse facilitation (PPF), supporting the notion that the evoked events were monoquantal. However, during paired-pulse depression (PPD), there was a significant decrease in unitary quantal size, which was not due to postsynaptic receptor desensitization. This asymmetry of quantal modulation during PPF and PPD was demonstrated at the same single synapse at different extracellular calcium concentrations. Our results indicate that PPF can be fully accounted for by an increase of release probability, whereas PPD may be caused by decreases in both release probability and quantal size. One possible explanation is that the release of a quantum of neurotransmitter from synaptic vesicles is not invariant but subject to rapid calcium-dependent modulation during short-term synaptic plasticity.
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See Commentary on page 907.
Contributed by Richard W. Tsien, November 18, 2003
Abbreviations: PPM, paired-pulse modulation; PPF, paired-pulse facilitation; PPD, paired-pulse depression; EPSC, excitatory postsynaptic current; mEPSC, miniature EPSC; CV, coefficient of variation; Pr, release probability; [Ca2+]o, external Ca2+.
To whom correspondence should be addressed. E-mail: rwtsien@stanford.edu.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0307149101