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Multivesicular release at developing Schaffer collateral-CA1 synapses: an analytic approach to describe experimental

F Ricci-Tersenghi1, F Minneci, E Sola

  • 1Dipartimento di Fisica Umana e Farmacologia, University La Sapienza, Piazzale A Rome, Italy.

Journal of Neurophysiology
|April 7, 2006
PubMed
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A new stochastic model distinguishes univesicular from multivesicular glutamate release. Results support multivesicular release at neonatal rat hippocampus synapses, indicating multiple vesicles release per action potential.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Biophysics

Background:

  • Glutamate release is crucial for synaptic transmission.
  • Understanding the mechanism of glutamate release (univesicular vs. multivesicular) is vital.
  • Existing models may not fully capture the dynamics of vesicle release.

Purpose of the Study:

  • To develop and validate a general stochastic model to differentiate univesicular and multivesicular release modes.
  • To provide analytical expressions for experimentally measurable quantities.
  • To determine model parameters and validate the model at specific synapses.

Main Methods:

  • Development of a simple, general stochastic model for vesicle release.
  • Analytical solution of the model to derive mathematical expressions.

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  • Experimental validation using glutamatergic CA3-CA1 synapses in neonatal rat hippocampus.
  • Analysis of synaptic response variability, potency ratios, and calcium concentration effects.

    • Main Results:

    • The model successfully discriminates between univesicular and multivesicular release.
    • Results strongly support a multivesicular release process at the studied synapses.
    • Estimated mean single vesicle release amplitude (q) of 5-10 pA, consistent with experiments.
    • Evidence supporting multivesicular release includes high amplitude variability, potency ratio >1, and calcium-dependent response changes.

    Conclusions:

    • The developed stochastic model is effective for distinguishing glutamate release modes.
    • Synaptic transmission at neonatal rat hippocampus Schaffer collateral-CA1 synapses predominantly follows a multivesicular release pattern.
    • A single action potential can trigger the release of multiple vesicles from the same release site.