Article Information

• PDF (1217 kb)

PubMed

• Articles by V.V. Uteshev
• Articles by P.S. Pennefather

Related Articles

• Exocytosis: A Molecular and Physiological Perspective

  Exocytosis: A Molecular and Physiological Perspective Neuron, Volume 17, Issue 6, 1 December 1996, Pages 1049-1055 Robert S Zucker Full Text | PDF (397 kb)

• Synaptic plasticity: Keeping synapses under control

  Synaptic plasticity: Keeping synapses under control Current Biology, Volume 8, Issue 16, 30 July 1998, Pages R564-R567 Lynn T Landmesser Summary Recent studies have confirmed that a retrograde signal is produced at the neuromuscular junction that can adjust the efficacy of transmission to meet long-term changing needs. Genetic manipulations in have begun to define the circumstances in which such signals are generated and how they act. Summary | Full Text | PDF (1215 kb)

• Synaptic transmission: Exciting times for presynaptic recept...

  Synaptic transmission: Exciting times for presynaptic receptors Current Biology, Volume 11, Issue 17, 4 September 2001, Pages R695-R697 Harald Vitten and Jeffry S Isaacson Summary Presynaptic receptors play an important role — typically inhibitory — in modulating the strength of synaptic transmission in the brain. Recent studies now reveal that neurotransmitters can enhance synaptic strength by activating ligand-gated ion channels in presynaptic nerve endings. Summary | Full Text | PDF (39 kb)

• …more

Abstract

Variation in the amplitude of miniature postsynaptic currents (mPSCs) generated by individual quanta of neurotransmitter is a major contributor to the variance of evoked synaptic responses. Here we explore the possible origins of this variability by developing a mathematical description of mPSC generation and consider the contribution of "off-center" release to this variability. By "off-center" release we mean variation in the distance between the position where a presynaptic vesicle discharges its content of neurotransmitter into the synaptic cleft and the center of a cluster of postsynaptic receptors (PRCs) that responds to those transmitter molecules by generating an mPSC. We show that when the time course of quantal discharge through a fusion pore (noninstantaneous release) is considered, elementary analytical descriptions of the subsequent diffusion of transmitter within the synaptic cleft (with or without uptake) predict the development of significant gradients of transmitter concentration during the rising phase of mPSCs. This description of diffusion is combined with a description of the pharmacodynamics of receptors in the PRC and of the time dependence of the gradient of transmitter concentration over the area of the PRC to reconstruct the time course and amplitude of an mPSC for a synapse of a given geometry. Within the constraints of known dimensions of presynaptic active zones and postsynaptic receptor clusters at CNS synapses, our analysis suggests that "off-center" release, produced by allowing release to occur anywhere within an anatomically defined presynaptic active zone, can be an important contributor to mPSC variability. Indeed, modulation of the influence of "off-center" release may be a novel way of controlling synaptic efficacy. We also show how noninstantaneous release can serve to focus the action of neurotransmitter within a given synapse and thereby reduce cross-talk between synapses.