Armitage B A, Siegelbaum S A
Center for Neurobiology and Behavior, Department of Pharmacology, Columbia University, Howard Hughes Medical Institute, New York, New York 10032, USA.
J Neurosci. 1998 Nov 1;18(21):8770-9. doi: 10.1523/JNEUROSCI.18-21-08770.1998.
The cellular mechanisms underlying the induction and expression of homosynaptic depression at the glutamatergic synapse between Aplysia sensory and motor neurons were studied in dissociated cell culture. Intracellular microelectrodes were used to stimulate action potentials in the presynaptic sensory neuron and record the depolarizing EPSP from the motor neuron. Homosynaptic depression (HSD) was induced by repeatedly stimulating the sensory neuron at rates as low as one action potential per minute. Activation of postsynaptic Glu receptors was neither sufficient nor necessary to induce HSD. Thus, repeated applications of exogenous Glu did not depress the synaptically evoked EPSP. Moreover, normal HSD was observed when the sensory neuron was stimulated during a period when the Glu receptors were blocked with the antagonist DNQX. The induction of HSD is thus likely to occur within the presynaptic terminal. We explored the role of presynaptic calcium in the induction of HSD by injecting the sensory neuron with EGTA, a relatively slow calcium chelator that does not alter rapid release but effectively buffers the slow residual calcium transient thought to be important for plasticity. EGTA had little effect on HSD, indicating that residual Cai is not involved. HSD does not appear to involve a decrease in presynaptic calcium influx, because there was no change in the presynaptic calcium transient, measured by calcium indicator dyes, during HSD. We conclude that HSD is induced and expressed in the presynaptic terminal, possibly by a mechanism directly coupled to the release process.
在分离细胞培养中研究了海兔感觉神经元和运动神经元之间谷氨酸能突触处同突触抑制的诱导和表达的细胞机制。细胞内微电极用于刺激突触前感觉神经元中的动作电位，并记录运动神经元的去极化兴奋性突触后电位（EPSP）。通过以低至每分钟一个动作电位的速率反复刺激感觉神经元来诱导同突触抑制（HSD）。突触后谷氨酸受体的激活对于诱导HSD既不充分也不必要。因此，反复应用外源性谷氨酸不会抑制突触诱发的EPSP。此外，当用拮抗剂DNQX阻断谷氨酸受体的期间刺激感觉神经元时，观察到正常的HSD。因此，HSD的诱导可能发生在突触前终末内。我们通过向感觉神经元注射乙二醇双四乙酸（EGTA）来探索突触前钙在HSD诱导中的作用，EGTA是一种相对缓慢的钙螯合剂，它不会改变快速释放，但有效地缓冲了被认为对可塑性很重要的缓慢的残余钙瞬变。EGTA对HSD几乎没有影响，表明残余的胞内钙（Cai）不参与其中。HSD似乎不涉及突触前钙内流的减少，因为在HSD期间，用钙指示剂染料测量的突触前钙瞬变没有变化。我们得出结论，HSD在突触前终末被诱导和表达，可能是通过一种直接与释放过程偶联的机制。
