Biology of glutamate transmission in serotonin neurons

点击翻译按钮获取中文摘要

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.