Neurotrophins act at presynaptic terminals to activate synapses among cultured hippocampal neurons

被引:66
作者
Collin, C
Vicario-Abejon, C
Rubio, ME
Wenthold, RJ
McKay, RDG
Segal, M [1 ]
机构
[1] Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel
[2] NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA
[3] Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD 20892 USA
关键词
BDNF; culture; hippocampus; NT-3; rat synapse;
D O I
10.1046/j.0953-816x.2001.01500.x
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
We have recently demonstrated that embryonic E16 hippocampal neurons grown in cultures are unable to form fast synaptic connections unless treated with BDNF or NT-3, This experimental system offers an opportunity to define the roles of neurotrophins in processes leading to formation of functional synaptic connections. We have used ultrastructural and electrophysiological methods to explore the cellular locations underlying neurotrophin action on synaptic maturation. The rate of spontaneous miniature excitatory postsynaptic currents (mEPSCs) evoked by hyperosmotic stimulation was 7-16-fold higher in neurotrophin-treated cells than in controls. In addition, the potent neurotransmitter-releasing drug alpha -latrotoxin was virtually ineffective in the control cells while it stimulated synaptic events in neurotrophin-treated cells. Likewise, the membrane-bound dye FM1-43 was taken up by terminals in neurotrophin-treated cultures five-fold more than in controls. Both the total number and the number of docked synaptic vesicles were increased by neurotrophin treatment. Activation of synaptic responses by neurotrophins occurred even when postsynaptic glutamate receptors and action potential discharges were pharmacologically blocked. These results are consistent with a presynaptic locus of action of neurotrophins to increase synaptic vesicle density which is critical for rapid synaptic transmission. They also suggest that neurotrophins can activate synapses in the absence of pre- and postsynaptic neuronal activity.
引用
收藏
页码:1273 / 1282
页数:10
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