Presynaptic Facilitation of Synaptic Transmission in the Hippocampus

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Abstract

Biochemical and genetic characterization of proteins in presynaptic axon terminals have led to models of the biochemical pathways underlying synaptic vesicle docking, activation, and fusion. Several studies have attempted recently to assign a precise physiological role to these proteins. This review deals with some of these studies, concentrating on those performed with hippocampal synapses. It is shown that changes in the state of these presynaptic proteins, together with modifications in Ca2+ dynamics in axon terminals, functionally determine the level of basal synaptic transmission, and underlie pharmacologically induced and activity-dependent facilitation of transmitter release in the central nervous system. 〈SCap>pharmacol. ther.〈Default ¶ Font> 77(3):203–223, 1998.

Section snippets

Introduction. synaptic transmission: a presynaptic point of view

In the CNS, neurons form connections at highly specialized sites called synapses. The synaptic cleft, the physical space between presynaptic and postsynaptic neurons, is very narrow, in the range of 30–50 nm. Synaptic transmission at the majority of synapses in the brain is mediated by the interaction of a chemical signal, the neurotransmitter, which is released from the presynaptic terminal in response to an electrical impulse, the action potential, with receptors within the postsynaptic

Cell biology of the axon terminal

The mechanisms by which the entry of Ca2+ triggers synaptic vesicle fusion and release of neurotransmitter are still poorly understood. Great progress has been made in identifying an ever growing number of proteins that are specifically localized to neuronal axon terminals, and that are believed to be involved in synaptic vesicle exocytosis and endocytosis. One important aspect of this work is the realization that neuronal exocytosis is a specialized aspect of the more general process of

Treatments that increase transmitter release in the hippocampus

Relatively few agents that enhance transmitter release have been studied at hippocampal synapses to date, in spite of the fact that the hippocampus is the area of the brain in which plastic changes in synaptic strength have been most thoroughly studied. At the NMJ, in contrast, the potential mechanisms of action of agents causing increases in acetylcholine release have been extensively investigated (reviewed byVan der Kloot and Molgó 1994). In addition, studies on the short-term presynaptic

Presynaptic proteins and plasticity

Synaptic vesicle fusion with the plasma membrane and neurotransmitter release are triggered by an action potential-mediated increase in the concentration of Ca2+ at special release sites of axon terminals called active zones (Katz 1969). Ca2+, therefore, couples the stimulus, the action potential, with the response, secretion. This stimulus-secretion coupling, however, is not static. The arrival of the action potential at the axon terminal may elicit a different response, depending on prior

Conclusions

In summary, functional observations support the hypothesis that presynaptic proteins are involved not only in basal, spontaneous and action potential-evoked release, but also in Ca2+-independent release and in short- and long-term synaptic plasticity. In addition, some of these proteins are the targets of clostridial neurotoxins and α-LTx. The actions of clostridial toxins indicate that the SNARE proteins are the core of the exocytotic machinery, as revealed in both biochemical and

Acknowledgements

I want to thank Beat Gähwiler and Scott Thompson for their tireless guidance, valuable advice and kindness. I have also benefited from the excellent assistance of the staff of Brain Research Institute, University of Zurich, especially Lucette Heeb, Eva Hochreutener, Rudolf Kägi, Hansjörg Kasper, Lotty Rietschin, Hans-Peter Rothenbühler, Roland Schöb, and Elisabeth Vollenweider. I acknowledge the financial support granted by the Dr. Eric Slack-Gyr Foundation and the Swiss National Science

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