Laboratory for Molecular Signalling, Babraham Institute, Babraham, Cambridge, United Kingdom.
Glia. 2011 Jan;59(1):82-93. doi: 10.1002/glia.21078. Epub 2010 Oct 21.
Classical synaptic transmission occurs at active zones within the synaptic cleft, but increasing evidence suggests that vesicle fusion can also occur outside of these zones, releasing transmitter directly into the extrasynaptic space. The role of such "ectopic" release is unclear, but in the cerebellar molecular layer it is thought to guide the processes of Bergmann glia toward synaptic terminals through activation of glial α-amino-3-hydroxyl-5-methyl-4-isoxazolepropionate (AMPA) receptors. Once surrounding the terminal, the glial process is presumed to limit spillover of neurotransmitter between synapses by rapid uptake of glutamate. We have previously reported that this route for neuron-glial transmission exhibits long-term depression following repetitive stimulation at frequencies in the 0.1-1 Hz range, in ex vivo slices from rat cerebellum. Here, we present evidence that LTD arises because ectopic sites lack the fast recycling mechanisms that operate at the active zone. Consequently, ectopic vesicles constitute an exhaustible pool that is depleted at normal synaptic firing rates and only recovers slowly. This effect is cumulative, meaning that the strength of ectopic transmission provides a read-out of the average frequency of presynaptic firing over several minutes. Glial processes are therefore likely to interact most closely with terminals that fire infrequently; conditions that may promote elimination of, rather than support for, the connection.
经典的突触传递发生在突触间隙的活性区，但越来越多的证据表明，囊泡融合也可以发生在这些区域之外，将递质直接释放到突触外空间。这种“异位”释放的作用尚不清楚，但在小脑分子层，它被认为通过激活神经胶质 α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体，引导伯格曼神经胶质细胞的过程朝向突触末端。一旦围绕着末端，胶质过程被认为通过谷氨酸的快速摄取来限制神经递质在突触之间的溢出。我们之前曾报道过，在来自大鼠小脑的离体切片中，重复刺激频率在 0.1-1 Hz 范围内，这种神经元-神经胶质传递途径会出现长时程抑郁。在这里，我们提供的证据表明，LTD 的产生是因为异位部位缺乏在活性区起作用的快速再循环机制。因此，异位囊泡构成一个可耗尽的池，在正常的突触放电率下被耗尽，并且恢复缓慢。这种效应是累积的，这意味着异位传递的强度提供了突触前放电频率的平均值的读数，在几分钟内。因此，神经胶质过程很可能与放电频率较低的末端最密切地相互作用；这些条件可能促进连接的消除，而不是支持。
