Modulation of neurotransmitter release at central synapses: role of endocannabinoids and transporters

在大脑中，大多数神经元(神经细胞)通过将化学物质(如氨基酸谷氨酸)释放到神经元(突触)之间的狭窄缝隙中来相互通信。谷氨酸穿过缝隙，在下一个细胞中发出信号。释放后，谷氨酸被吸入并循环到神经细胞中重复使用。记忆和学习是突触上这种信号变化的结果。突触密密麻麻地堆积在一起，因此从一个神经元释放的谷氨酸可以扩散到邻近的突触，而不是它应该发出的信号。这种所谓的突触串扰会降低大脑的信息存储能力。我已经发现了一种检测突触串扰的探测器，它可以让神经元释放另一种名为大麻素的化学物质(与大麻有关)，这种化学物质通过减少谷氨酸的释放来减少突触串扰。我正在研究控制谷氨酸释放的两个基本机制：(1)减少谷氨酸释放包数量的大麻素系统；(2)将谷氨酸循环到释放神经元，控制每包谷氨酸释放的谷氨酸量。了解谷氨酸的释放是如何控制的，对于了解大脑的正常功能和病理条件下的问题至关重要。

In the brain, most neurons (nerve cells) communicate with each other by releasing packets of a chemical, such as the amino acid glutamate, into the narrow gap between the neurons (the synapse). The glutamate passes across the gap and initiates a signal in the next cell. After release the glutamate is hoovered up and recycled to the nerve cell for re-use. Memory and learning occur as a result of alterations of this signalling at synapses. Synapses are densely packed so that glutamate released from one neuron can spread to neighbouring synapses that it was not supposed to signal to. This so-called synaptic crosstalk degrades the brain‘s information storage capacity. I have identified a detector of synaptic crosstalk, which makes neurons release another chemical called a cannabinoid (related to cannabis), which decreases synaptic crosstalk by reducing glutamate release. I am studying two fundamental mechanisms controlling glutamate release: (1) the cannabinoid system which reduces the number of packets of glutamate released; (2) the recycling of glutamate to releasing neurons which controls the amount of glutamate released from each packet. Understanding how glutamate release is controlled is essential to understand the normal function of the brain and what goes wrong in pathological conditions.