Lovell P, McMahon B, Syed N I
Department of Cell Biology and Anatomy and Biological Sciences, Respiratory and Neuroscience Research Groups, Faculty of Medicine, The University of Calgary, Calgary, Alberta T2N 4N1, Canada.
J Neurophysiol. 2002 Sep;88(3):1328-38. doi: 10.1152/jn.2002.88.3.1328.
The cellular mechanisms that determine specificity of synaptic connections between mutually connected neurons in the nervous system have not yet been fully examined in vertebrate and invertebrate species. Here we report on a novel form of synaptic interaction during early stages of synapse formation between reciprocally connected Lymnaea neurons. Specifically, using soma-soma synapses between an identified dopaminergic neuron (also known as the giant dopamine cell), right pedal dorsal 1 (RPeD1), and a FMRFamidergic neuron, visceral dorsal 4 (VD4), we demonstrate that although reciprocal inhibitory synapses re-form between the somata after 24-36 h of pairing, VD4 is, however, the first cell to establish synaptic contacts with RPeD1 (within 12-18 h). We show that VD4 "captures" RPeD1 first as a postsynaptic cell by suppressing its transmitter secretory machinery during early stages of cell-cell pairing. The VD4-induced suppression of transmitter release from RPeD1 was transient, and it required transcription and de novo protein synthesis dependent step in VD4 but not in RPeD1. The VD4-induced effects on RPeD1 were mimicked by a FMRFamide-like peptide. Perturbation of FMRFamide-activated metabolites of the arachidonic acid pathway in RPeD1 not only prevented FMRFamide-induced suppression of transmitter release from the giant dopamine cell but also shifted the synaptic balance in favor of RPeD1, thus making it the first cell to begin synaptic transmission with VD4 within 12-18 h. A single RPeD1 that had developed dopamine secretory capabilities overnight and was subsequently paired with VD4 for 12-18 h was, however, immune to VD4-induced suppression of transmitter release. Under these experimental conditions, both cells developed mutual inhibitory synapses concurrently. Taken together, our data provide evidence for novel synaptic interaction between reciprocally connected neurons and underscore the importance of transmitter-receptor interplay in regulating the timing of synapse formation in the nervous system.
在脊椎动物和无脊椎动物中，尚未充分研究决定神经系统中相互连接的神经元之间突触连接特异性的细胞机制。在此，我们报告了相互连接的椎实螺神经元在突触形成早期阶段的一种新型突触相互作用形式。具体而言，利用已鉴定的多巴胺能神经元（也称为巨大多巴胺细胞）右足背侧1（RPeD1）和FMRF酰胺能神经元内脏背侧4（VD4）之间的体细胞 - 体细胞突触，我们证明，虽然配对24 - 36小时后，体细胞之间会重新形成相互抑制性突触，但VD4却是第一个与RPeD1建立突触接触的细胞（在12 - 18小时内）。我们表明，在细胞 - 细胞配对的早期阶段，VD4通过抑制其递质分泌机制，首先将RPeD1“捕获”为突触后细胞。VD4诱导的RPeD1递质释放抑制是短暂的，并且它需要VD4中依赖转录和从头合成蛋白质的步骤，而RPeD1则不需要。FMRF酰胺样肽可模拟VD4对RPeD1的诱导作用。RPeD1中FMRF酰胺激活的花生四烯酸途径代谢产物的扰动不仅阻止了FMRF酰胺诱导的巨大多巴胺细胞递质释放抑制，还使突触平衡向有利于RPeD1的方向转变，从而使其成为在12 - 18小时内第一个开始与VD4进行突触传递的细胞。然而，一个在一夜之间已发展出多巴胺分泌能力并随后与VD4配对12 - 18小时的单个RPeD1，对VD4诱导的递质释放抑制具有抗性。在这些实验条件下，两个细胞同时发展出相互抑制性突触。综上所述，我们的数据为相互连接的神经元之间的新型突触相互作用提供了证据，并强调了递质 - 受体相互作用在调节神经系统突触形成时间方面的重要性。
