Journal of Neurophysiology, Vol 75, Issue 6 2451-2466, Copyright © 1996 by APS

ARTICLES

Synaptic structural complexity as a factor enhancing probability of calcium-mediated transmitter release

R. L. Cooper, J. L. Winslow, C. K. Govind and H. L. Atwood
Department of Physiology, Scarborough College, University of Toronto, Canada.

1. In a model synaptic system, the excitatory neuromuscular junction of the freshwater crayfish, the nerve terminals possess synapses that vary in structural complexity, with numbers of active zones ranging from zero to five. Active zones on individual synapses show a wide range of separation distances. We tested the hypothesis that two active zones of a single synapse in close proximity can enhance the localized increase in free calcium ion concentration, thus enhancing the probability of neurotransmission at that synapse. We evaluated the increase in calcium ion concentration as a function of distance between adjacent active zones. 2. To test this hypothesis, a reaction-diffusion model for Ca2+ entering the presynaptic terminals was used. This test was used because 1) present measurement techniques are inadequate to resolve quantitatively the highly localized, transient calcium microdomains at synaptic active zones; and 2) there is presently no suitable preparation for physiological recording from isolated synapses with varying distances between active zones. Included in the model were intracellular buffer and a typical distribution of voltage-activated Ca2+ channels for an active zone, estimated from freeze-fracture micrographs. 3. The model indicated that localized Ca2+ clouds from discrete active zones can overlap to create spatial enhancement of Ca2+ concentration. The degree of interaction between two active zones depends on the distance between them. When two typical active zones are separated by < or = 200 nm, the maximum intracellular Ca2+ concentration ([Ca2+]i) is greater at 1) the midpoint between them, and 2) the center of each one, than at the corresponding positions for a single isolated active zone. Enhanced [Ca2+]i at the edge of the active zone where "docked" synaptic vesicles occur would be expected to have an effect on transmitter release. 4. When the model includes no intracellular buffer, the increase in [Ca2+]i is a linear function of calcium channel current, but is a nonlinear function of the number of conducting calcium channels in an active zone. With immobile buffer included, the increase in [Ca2+]i is nonlinear with respect to both channel current and number of conducting channels. 5. Inclusion of immobile buffer in the model provides "released" residual calcium that slowly accumulates during a train of current pulses. Released residual calcium accumulates more rapidly at paired active zones separated by < or = 200 nm that at single isolated active zones. 6. We propose that the probability of release is enhanced at synapses with closely associated active zones. Synapses of this type ("complex" synapses) could be selectively recruited when the neuron is active at low frequencies. At higher frequencies of neuronal activity, more distant active zones may interact and acquire a greater probability of releasing quanta. This would provide the nerve terminal with one component of a mechanism for frequency facilitation, because the number of quanta released by the terminal as a whole would increase with frequency. Thus variation in synaptic complexity in a nerve terminal provides a mechanism for short-term plasticity of transmitter release.

This article has been cited by other articles:

				S. Logsdon, A. F. M. Johnstone, K. Viele, and R. L. Cooper Regulation of synaptic vesicles pools within motor nerve terminals during short-term facilitation and neuromodulation J Appl Physiol, February 1, 2006; 100(2): 662 - 671. [Abstract] [Full Text] [PDF]

				H. Photowala, R. Freed, and S. Alford Location and function of vesicle clusters, active zones and Ca2+ channels in the lamprey presynaptic terminal J. Physiol., November 15, 2005; 569(1): 119 - 135. [Abstract] [Full Text] [PDF]

				V. Shahrezaei and K. R. Delaney Consequences of Molecular-Level Ca2+ Channel and Synaptic Vesicle Colocalization for the Ca2+ Microdomain and Neurotransmitter Exocytosis: A Monte Carlo Study Biophys. J., October 1, 2004; 87(4): 2352 - 2364. [Abstract] [Full Text] [PDF]

				G. M. Sparks and R. L. Cooper 5-HT offsets homeostasis of synaptic transmission during short-term facilitation J Appl Physiol, May 1, 2004; 96(5): 1681 - 1690. [Abstract] [Full Text] [PDF]

				M. R. Bennett, L. Farnell, and W. G. Gibson The Facilitated Probability of Quantal Secretion within an Array of Calcium Channels of an Active Zone at the Amphibian Neuromuscular Junction Biophys. J., May 1, 2004; 86(5): 2674 - 2690. [Abstract] [Full Text] [PDF]

				V. Matveev, R. S. Zucker, and A. Sherman Facilitation through Buffer Saturation: Constraints on Endogenous Buffering Properties Biophys. J., May 1, 2004; 86(5): 2691 - 2709. [Abstract] [Full Text] [PDF]

				A. G. Millar and H. L. Atwood Crustacean Phasic and Tonic Motor Neurons Integr. Comp. Biol., February 1, 2004; 44(1): 4 - 13. [Abstract] [Full Text] [PDF]

				S. J. Sigrist, D. F. Reiff, P. R. Thiel, J. R. Steinert, and C. M. Schuster Experience-Dependent Strengthening of Drosophila Neuromuscular Junctions J. Neurosci., July 23, 2003; 23(16): 6546 - 6556. [Abstract] [Full Text] [PDF]

				D. F. Reiff, P. R. Thiel, and C. M. Schuster Differential Regulation of Active Zone Density during Long-Term Strengthening of Drosophila Neuromuscular Junctions J. Neurosci., November 1, 2002; 22(21): 9399 - 9409. [Abstract] [Full Text] [PDF]

				S. J. Sigrist, P. R. Thiel, D. F. Reiff, and C. M. Schuster The Postsynaptic Glutamate Receptor Subunit DGluR-IIA Mediates Long-Term Plasticity in Drosophila J. Neurosci., September 1, 2002; 22(17): 7362 - 7372. [Abstract] [Full Text] [PDF]

				C. J. Meinrenken, J. G. G. Borst, and B. Sakmann Calcium Secretion Coupling at Calyx of Held Governed by Nonuniform Channel-Vesicle Topography J. Neurosci., March 1, 2002; 22(5): 1648 - 1667. [Abstract] [Full Text] [PDF]

				D. L. Mykles, S. Medler, A. Koenders, and R. Cooper Myofibrillar protein isoform expression is correlated with synaptic efficacy in slow fibres of the claw and leg opener muscles of crayfish and lobster J. Exp. Biol., February 15, 2002; 205(4): 513 - 522. [Abstract] [Full Text] [PDF]

				M. E. Crider and R. L. Cooper Differential facilitation of high- and low-output nerve terminals from a single motoneuron J Appl Physiol, March 1, 2000; 88(3): 987 - 996. [Abstract] [Full Text] [PDF]

				H Aonuma, T Nagayama, and M Takahata Modulatory effects of nitric oxide on synaptic depression in the crayfish neuromuscular system J. Exp. Biol., January 12, 2000; 203(23): 3595 - 3602. [Abstract] [PDF]

				P. He, R. C. Southard, D. Chen, S. W. Whiteheart, and R. L. Cooper Role of alpha -SNAP in Promoting Efficient Neurotransmission at the Crayfish Neuromuscular Junction J Neurophysiol, December 1, 1999; 82(6): 3406 - 3416. [Abstract] [Full Text] [PDF]

				H. L. Atwood and J. M. Wojtowicz Silent Synapses in Neural Plasticity: Current Evidence Learn. Mem., November 1, 1999; 6(6): 542 - 571. [Abstract] [Full Text]

				D. A. DiGregorio, A. Peskoff, and J. L. Vergara Measurement of Action Potential-Induced Presynaptic Calcium Domains at a Cultured Neuromuscular Junction J. Neurosci., September 15, 1999; 19(18): 7846 - 7859. [Abstract] [Full Text] [PDF]

				M. E. Ruffner, S. I. Cromarty, and R. L. Cooper Depression of Synaptic Efficacy in High- and Low-Output Drosophila Neuromuscular Junctions by the Molting Hormone (20-HE) J Neurophysiol, February 1, 1999; 81(2): 788 - 794. [Abstract] [Full Text] [PDF]

				P. A. Quigley, M. Msghina, C. K. Govind, and H. L. Atwood Visible Evidence for Differences in Synaptic Effectiveness With Activity-Dependent Vesicular Uptake and Release of FM1-43 J Neurophysiol, January 1, 1999; 81(1): 356 - 370. [Abstract] [Full Text] [PDF]

				R. L. Cooper and M. E. Ruffner Depression of Synaptic Efficacy at Intermolt in Crayfish Neuromuscular Junctions by 20-Hydroxyecdysone, a Molting Hormone J Neurophysiol, April 1, 1998; 79(4): 1931 - 1941. [Abstract] [Full Text] [PDF]

				M. Msghina, C. K. Govind, and H. L. Atwood Synaptic Structure and Transmitter Release in Crustacean Phasic and Tonic Motor Neurons J. Neurosci., February 15, 1998; 18(4): 1374 - 1382. [Abstract] [Full Text] [PDF]

				H. von Gersdorff and G. Matthews Depletion and Replenishment of Vesicle Pools at a Ribbon-Type Synaptic Terminal J. Neurosci., March 15, 1997; 17(6): 1919 - 1927. [Abstract] [Full Text] [PDF]

				P. A. Salin, M. Scanziani, R. C. Malenka, and R. A. Nicoll Distinct short-term plasticity at two excitatory synapses in the hippocampus PNAS, November 12, 1996; 93(23): 13304 - 13309. [Abstract] [Full Text] [PDF]