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Stochastic Modeling of Facilitated Neurosecretion

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Abstract

Two models of neurosecretion were evaluated in terms of their ability to predict the dependency of quantal content (m) on the frequency of repetitive stimulation of a lobster motoneuron. First, the hypothesis that neurosecretion is limited by a fixed number of release sites was tested by the fit of the distribution of m by uniform and nonuniform binomial statistics. The obtained release probabilities suggest that frequency facilitation can be due to activation of a group of sites with high release probabilities. However, the fit obtained using this model is not statistically significant due to a large number of fitting parameters. Second, the hypothesis that neurosecretion is limited by the rates of exchange between the releasable pool and the total store of quanta and that each stimulus enhances quantal mobilization was tested. Monte Carlo simulation was carried out in accordance with this model and reproduced the observed distribution of m with very few fitting parameters and therefore with a high level of significance (>0.1). This result demonstrates that mobilization of extra vesicles with each stimulus is a mechanism that allows a very accurate and parsimonious quantitative description of frequency facilitation.

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References

  • Augustine GJ, Charlton MP, Smith SJ (1987) Calcium action in synaptic transmitter release. Ann. Rev. Neurosci. 10:633–693.

    PubMed  Google Scholar 

  • Bennett MR, Robinson J (1990) Probabilistic secretion of quanta from nerve terminals at synaptic sites on muscle cells: Nonuniformity, autoinhibition and the binomial hypothesis. Proc. Rol. Lond. 239:329–358.

    Google Scholar 

  • Bertram R, Sherman A, Stanley EF (1996) Single-domain/bound calcium hypothesis of transmitter release and facilitation. J. Neurophysiol. 75:1919–1931.

    PubMed  Google Scholar 

  • Blundon JA, Wright SN, Brodwick MS, Bittner GD (1993) Residual free calcium is not responsible for facilitation of neurotransmitter release. PNAS 90(20):9388–9392.

    PubMed  Google Scholar 

  • Bykhovskaia M, Hackett JT, Worden MK (1999) Asynchrony of quantal events in evoked multiquantal responses. J. Neurophysiol. 81:2234–2242.

    PubMed  Google Scholar 

  • Bykhovskaia M, Worden MK, Hackett JT (1996) An algorithm for high resolution detection of postsynaptic quantal events in extracellular records. J. Neurosci. Methods. 65:173–182.

    PubMed  Google Scholar 

  • Bykhovskaia M, Hackett JT, Worden MK (1999) Asynchrony of quantal events in evoked multiquantal responses indicates presynaptic quantal interaction. J. Neurophysiol. 81:2234–2242.

    PubMed  Google Scholar 

  • Cooper RL, Marin L, Atwood HL (1995) Synaptic differentiation of a single motor neuron: Conjoint definition of transmitter release, presynaptic calcium signals and ultrastructure. J. Neurosci. 15:4209–4222.

    PubMed  Google Scholar 

  • Cooper RL, Winslow JL, Govind CK, Atwood HL (1996) Synaptic structural complexity as a factor enhancing probability of calcium mediated transmitter release. J. Neurophysiol. 75:2451–2466.

    PubMed  Google Scholar 

  • Delaney KR, Tank DW (1994) A quantitative measurement of the dependence of short-term synaptic enhancement on presynaptic residual calcium. J. Neurosci. 14(10):5885–5902.

    PubMed  Google Scholar 

  • Dobrunz LE, Stevens CF (1997) Heterogeneity of release probability, facilitation, and depletion at central synapses. Neuron. 18:995–1008.

    PubMed  Google Scholar 

  • Elmqvist D, Quastel DMJ (1965) A quantitative study of end-plate potentials in isolated human muscle. J. Physiol. 178:505–529.

    PubMed  Google Scholar 

  • Hubbard JI (1963) Repetitive stimulation at the mammalian neuromuscular junction, and the mobilization of transmitter. J. Physiol. 169:641–662.

    PubMed  Google Scholar 

  • Jonson EW, Wernig A (1971) The binomial nature of transmitter release in the crayfish neuromuscular junction. J. Physiol. 218:757–767.

    PubMed  Google Scholar 

  • Kamiya H, Zucker RS (1994) Residual calcium and short-term synaptic plasticity. Nature 371:603–606.

    PubMed  Google Scholar 

  • Katz B (1969) The release of neural transmitter substances. Liverpool University Press, Liverpool.

    Google Scholar 

  • Katz B, Miledi R (1968) The role of calcium in neuromuscular facilitation. J. Physiolol. 195:481–492.

    Google Scholar 

  • Korn H, Mallet A, Triller A, Faber DS (1982) Transmission at a central inhibitory synapse. II. Quantal description of release, with a physical correlate for binomial n. J. Neurophysiol. 48:679–707.

    PubMed  Google Scholar 

  • Maeno T, Edwards C (1969) Neuromuscular facilitation with low-frequency stimulation and effects of some drugs. J. Neurophysiol. 32:785–791.

    PubMed  Google Scholar 

  • Mallart A, Martin AR (1967) An analysis of facilitation of transmitter release at the neuromuscular junction of a frog. J. Physiol. 193:679–694.

    Google Scholar 

  • Redman S (1990) Quantal analysis of synaptic potentials in neurons of the central nervous system. Physiol. Rev. 70:165–198.

    PubMed  Google Scholar 

  • Rosenmund C, Stevens CF (1996) Definition of the readily releasable pool of vesicles at hippocampal synapses. Neuron. 16:1197–1207.

    PubMed  Google Scholar 

  • Schikorski T, Stevens CF (1997) Quantitative ultrastructural analysis of hippocampal excitatory synapses. J. Neurosci. 17(15): 5858–5867.

    PubMed  Google Scholar 

  • Smith BR, Wojtowicz JM, Atwood HL (1991) Maximum likelihood estimation of non-uniform transmitter release probabilities at the crayfish neuromuscular junction. J. Theor. Biol. 150:457–472.

    PubMed  Google Scholar 

  • Stevens CF, Wesseling JF (1998) Activity-dependent modulation of the rate at which synaptic vesicles become available to undergo exocytosis. Neuron. 21:415–424.

    PubMed  Google Scholar 

  • Stricker C, Redman S (1994) Statistical models of synaptic transmission evaluated using the expectation-maximization algorithm. Biophys. J. 67:656–670.

    PubMed  Google Scholar 

  • Vere-Jones D (1966) Simple stochastic models for the release of quanta of transmitter from a nerve terminal. Australian J. Stat. 8(2):53–63.

    Google Scholar 

  • Wernig A (1972) Changes in statistical parameters during facilitation at the crayfish neuromuscular junction. J. Physiol. Lond. 226:751–759.

    PubMed  Google Scholar 

  • Winslow JL, Duffy SN, Charlton MP (1994) Homosynaptic facilitation of transmitter release in crayfish is not affected by mobile calcium chelators: Implications for the residual ionized calcium hypothesis from electrophysiological and computational analysis. J. Neurophysiol. 72:1769–1777.

    PubMed  Google Scholar 

  • Wojtowicz JM, Smith BR, Atwood HL (1991) Activity-dependent recruitment of silent synapses. Ann. New York Acad. Sci. 627:169–179.

    Google Scholar 

  • Wojtowicz JM, Marin L, Atwood HL (1994) Activity-induced changes in synaptic release sites at the crayfish neuromuscular junction. J. Neurosci. 14:3688–3703.

    PubMed  Google Scholar 

  • Worden MK, Bykhovskaia M, Hackett JT (1997) Facilitation at the lobster neuromuscular junction: A stimulus-dependent mobilization model. J. Neurophysiol. 78:417–427.

    PubMed  Google Scholar 

  • Zucker RS (1973) Changes in the statistics of transmitter release during facilitation. J. Physiol. 229:787–810.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Molecular Physiology and Biological Physics, University of Virginia Health Sciences Center, Charlottesville, VA, 22906-0011

    Maria Bykhovskaia & John T. Hackett

  2. Department of Neuroscience, University of Virginia Health Sciences Center, Charlottesville, VA, 22906-0011

    Mary Kate Worden

Authors
  1. Maria Bykhovskaia
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  2. Mary Kate Worden
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  3. John T. Hackett
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Bykhovskaia, M., Worden, M.K. & Hackett, J.T. Stochastic Modeling of Facilitated Neurosecretion. J Comput Neurosci 8, 113–126 (2000). https://doi.org/10.1023/A:1008917130947

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