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Distinct Effects of Clostridial Toxins on Activity‐dependent Modulation of Autaptic Responses in Cultured Hippocampal Neurons
Author(s) -
OweLarsson Björn,
Kristensson Krister,
Hill Russell H.,
Brodin Lennart
Publication year - 1997
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.1997.tb01535.x
Subject(s) - neurotransmission , exocytosis , excitatory postsynaptic potential , hippocampal formation , stimulation , postsynaptic potential , biology , postsynaptic current , synaptic vesicle , neuroscience , chemistry , inhibitory postsynaptic potential , biophysics , biochemistry , vesicle , receptor , secretion , membrane
Clostridial neurotoxins proteolyse specific proteins implicated in synaptic vesicle exocytosis, but their actions on the release machinery in functional synapses is not well understood. Here we examine the effects of botulinum toxin A (BoNT/A) and tetanus toxin (TeTx) on autaptic transmission in cultured rat hippocampal neurons using whole‐cell voltage clamp recordings. The proportion of cells responding to stimulation with an excitatory postsynaptic current (EPSC) and the magnitude of the remaining responses decreased gradually with increasing concentration of either toxin. However, the activity‐dependent modulation (5 Hz repetitive stimulation) of EPSCs remaining after toxin inhibition differed markedly between the two toxins. The TeTx inhibition was associated with a persistent activity‐dependent depression similar to that in control cells. In contrast, the BoNT/A inhibition was accompanied by a reversal of the modulation into facilitation, resembling that induced by lowering of the calcium concentration. These results demonstrate a difference between BoNT/A and TeTx in their mode of inhibition of synaptic vesicle exocytosis, which suggests that they exert their preferential actions at distinct steps of the release process.