An evaluation of causes for unreliability of synaptic transmission (original) (raw)

Abstract

Transmission at individual synaptic contacts on CA1 hippocampal pyramidal neurons has been found to be very unreliable, with greater than half of the arriving presynaptic nerve impulses failing to evoke a postsynaptic response. This conclusion has been reached using the method of minimal stimulation of Schaffer collaterals and whole cell recording in hippocampal slices; with minimal stimulation only one or a few synapses are activated on the target neuron and the behavior of individual synapses can be examined. Four sources for the unreliability of synaptic transmission have been investigated: (i) the fluctuation of axon thresholds at the site of stimulation causing the failure to generate a nerve impulse in the appropriate Schaffer collaterals, (ii) the failure of nerve impulses generated at the site of stimulation to arrive at the synapse because of conduction failures at axon branch points, (iii) an artifactual synaptic unreliability due to performing experiments in vitro at temperatures well below the normal mammalian body temperature, and (iv) transmission failures due to probabilistic release mechanisms at synapses with a very low capacity to release transmitter. We eliminate the first three causes as significant contributions and conclude that probabilistic release mechanisms at low capacity synapses are the main cause of unreliability of synaptic transmission.

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Selected References

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  1. Bekkers J. M., Richerson G. B., Stevens C. F. Origin of variability in quantal size in cultured hippocampal neurons and hippocampal slices. Proc Natl Acad Sci U S A. 1990 Jul;87(14):5359–5362. doi: 10.1073/pnas.87.14.5359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Buhl E. H., Halasy K., Somogyi P. Diverse sources of hippocampal unitary inhibitory postsynaptic potentials and the number of synaptic release sites. Nature. 1994 Apr 28;368(6474):823–828. doi: 10.1038/368823a0. [DOI] [PubMed] [Google Scholar]
  3. Dodge F. A., Jr, Rahamimoff R. Co-operative action a calcium ions in transmitter release at the neuromuscular junction. J Physiol. 1967 Nov;193(2):419–432. doi: 10.1113/jphysiol.1967.sp008367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. FRANKENHAEUSER B., HODGKIN A. L. The action of calcium on the electrical properties of squid axons. J Physiol. 1957 Jul 11;137(2):218–244. doi: 10.1113/jphysiol.1957.sp005808. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Freund T. F., Martin K. A., Soltesz I., Somogyi P., Whitteridge D. Arborisation pattern and postsynaptic targets of physiologically identified thalamocortical afferents in striate cortex of the macaque monkey. J Comp Neurol. 1989 Nov 8;289(2):315–336. doi: 10.1002/cne.902890211. [DOI] [PubMed] [Google Scholar]
  6. Freund T. F., Martin K. A., Somogyi P., Whitteridge D. Innervation of cat visual areas 17 and 18 by physiologically identified X- and Y- type thalamic afferents. II. Identification of postsynaptic targets by GABA immunocytochemistry and Golgi impregnation. J Comp Neurol. 1985 Dec 8;242(2):275–291. doi: 10.1002/cne.902420209. [DOI] [PubMed] [Google Scholar]
  7. Gulyás A. I., Miles R., Sík A., Tóth K., Tamamaki N., Freund T. F. Hippocampal pyramidal cells excite inhibitory neurons through a single release site. Nature. 1993 Dec 16;366(6456):683–687. doi: 10.1038/366683a0. [DOI] [PubMed] [Google Scholar]
  8. Hessler N. A., Shirke A. M., Malinow R. The probability of transmitter release at a mammalian central synapse. Nature. 1993 Dec 9;366(6455):569–572. doi: 10.1038/366569a0. [DOI] [PubMed] [Google Scholar]
  9. Raastad Morten, Storm Johan F., Andersen Per. Putative Single Quantum and Single Fibre Excitatory Postsynaptic Currents Show Similar Amplitude Range and Variability in Rat Hippocampal Slices. Eur J Neurosci. 1992 Oct;4(1):113–117. doi: 10.1111/j.1460-9568.1992.tb00114.x. [DOI] [PubMed] [Google Scholar]
  10. Rosenmund C., Clements J. D., Westbrook G. L. Nonuniform probability of glutamate release at a hippocampal synapse. Science. 1993 Oct 29;262(5134):754–757. doi: 10.1126/science.7901909. [DOI] [PubMed] [Google Scholar]
  11. Sorra K. E., Harris K. M. Occurrence and three-dimensional structure of multiple synapses between individual radiatum axons and their target pyramidal cells in hippocampal area CA1. J Neurosci. 1993 Sep;13(9):3736–3748. doi: 10.1523/JNEUROSCI.13-09-03736.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Stevens C. F. Neuronal communication. Cooperativity of unreliable neurons. Curr Biol. 1994 Mar 1;4(3):268–269. doi: 10.1016/s0960-9822(00)00062-2. [DOI] [PubMed] [Google Scholar]
  13. Stevens C. F., Wang Y. Reversal of long-term potentiation by inhibitors of haem oxygenase. Nature. 1993 Jul 8;364(6433):147–149. doi: 10.1038/364147a0. [DOI] [PubMed] [Google Scholar]