Biology of glutamate transmission in serotonin neurons

神经细胞（神经元）使用一种叫做神经递质的分子来相互交流。长期以来，人们一直认为单个神经元只能产生和释放一种递质，但是，在过去的三十年里，发现了许多神经元双语甚至多语的例子。因此，我们对大脑中的单胺神经元释放兴奋性氨基酸谷氨酸感兴趣，这些神经元利用多巴胺、去甲肾上腺素或血清素作为神经递质。通过大量的神经生物学技术，从电子显微镜到单个神经元培养的电生理学，我们已经表征了多巴胺-谷氨酸神经元的许多形态特征和功能特性，特别是在发育过程中。这些研究提出了许多关于这种神经元通信的双重模式的问题。它什么时候出现？它是短暂的还是永久的？它是否受到监管？在什么情况下？它的特殊作用是什么？它是神经元树突生长和突触连接形成的决定因素吗？这两种递质是否都在包含它们的神经元的所有分支和/或末梢中储存和释放？在什么条件下，对他们的环境有什么影响？为了回答这些问题，我们现在将转向大脑中的5-羟色胺（5-羟色胺，5-HT）神经元，它最近被证明能够产生和释放谷氨酸。我们将在三种特别有趣的实验条件下研究这些神经元：i)在大鼠大脑中过度生长的模型；ii)经过基因改造（基因敲除）使其5-羟色胺神经元不能储存和释放谷氨酸的小鼠，iii)从这些小鼠而非其正常同类身上获得的血清素神经元培养物。由于这些准备工作，我们应该能够很好地阐明谷氨酸共释放在5-HT神经元生长过程中的形态发生作用，更广泛地说，为解释中枢神经系统单胺神经元谷氨酸共表型的功能意义阐述一个新的概念和启发式框架。

Nerve cells (neurons) use molecules called neurotransmitters to communicate with one another. It was long believed that a single neuron could produce and release only one transmitter, but, in the last thirty years, many examples of neuronal bilinguism, and even multilinguism, have been discovered. Hence our interest for the release of the excitatory amino acid glutamate by the monoamine neurons in brain, which utilize dopamine, noradrenaline or serotonin as neurotransmitter. By means of a vast array of neurobiological techniques, ranging from electron microscopy to electrophysiology in single neuron culture, we have characterize many of the morphological features and functional properties of the dopamine-glutamate neurons, notably during development. These studies have raised many questions regarding such a dual mode of neuronal communication. When does it appear? Is it transient or permanent? Is it regulated and under what circumstances? What is its particular role? Is it a determinant factor in the growth of neuronal arborizations and the formation of synaptic connections? Are both transmitters stored in and released from all branches and/or terminals of the neurons containing them? Under which conditions and with what consequences on their environment? To answer these questions, we will now turn to the serotonin (5-hydroxytryptamine, 5-HT) neurons in brain, which were very recently shown to be able to produce and release glutamate. We will study these neurons in three experimental conditions of particular interest: i) a model of excessive growth in the rat braint; ii) mice that have been genetically modified (knockout) so that their 5-HT neurons cannot store and release glutamate, and iii) cultures of serotonin neurons obtained from these mice rather than their normal congeners. Owing to these preparations, we should be in an excellent position to elucidate the morphogenic role of glutamate corelease during the growth or 5-HT neurons, and, more generally, to elaborate a new conceptual and heuristic framework for interpring the functional significance of the glutamate co-phenotype of monoamine neurons in the central nervous system.