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

中央突触神经递质释放的调节：内源性大麻素和转运蛋白的作用

• 批准号: G0600064/1
• 负责人: Paikan Marcaggi
• 金额: $ 141.59万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0600064%2F1
• 关键词: Modulation; neurotransmitter; release; central; synapses

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.

在大脑中，大多数神经元（神经细胞）通过向神经元之间的狭窄间隙（突触）释放化学物质（如谷氨酸）来相互交流。谷氨酸穿过差距并在下一个细胞中启动信号。释放后，谷氨酸被吸走并回收到神经细胞中重新使用。记忆和学习的发生是由于突触上这种信号的改变。突触是密集的，因此从一个神经元释放的谷氨酸可以扩散到相邻的突触，而这些突触本来不应该向其发出信号。这种所谓的突触串扰降低了大脑的信息存储能力。我已经确定了一种突触串扰的检测器，它使神经元释放另一种称为大麻素（与大麻有关）的化学物质，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种基本机制：（1）大麻素系统，它减少了释放的谷氨酸包的数量;（2）谷氨酸再循环到释放神经元，控制每个包释放的谷氨酸量。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以及病理条件下的错误至关重要。