Incomplete removal of extracellular glutamate controls synaptic transmission and integration at a cerebellar synapse.
Incomplete removal of extracellular glutamate controls synaptic transmission and integration at a cerebellar synapse.
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DOI：
10.7554/elife.63819
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发表时间：
2021-02-22
期刊：
影响因子：
7.7
通讯作者：
Trussell LO
中科院分区：
文献类型：
--
作者：
Balmer TS;Borges-Merjane C;Trussell LO
谷氨酸能苔藓纤维（MFs）与小脑单极刷细胞（UBCs）形成的突触会根据UBC大的树突刷上所表达的谷氨酸受体的组成情况，产生缓慢的兴奋性（ON）或抑制性（OFF）突触后反应。通过小鼠脑片记录以及对突触传递的计算建模，我们发现大量谷氨酸会保留在UBC突触间隙中，其含量足以改变OFF型UBC的自发放电，并使ON型UBC的AMPA受体产生持续性脱敏。这种环境谷氨酸的来源是MF末端自发的、不依赖动作电位的胞吐作用，其水平取决于谷氨酸转运体EAAT1 - 2的活性。环境谷氨酸水平的升高会改变ON型UBC诱发突触反应的极性，并改变对类似体内突触活动反应的时相。与经典的快速突触不同，UBC突触处的受体实际上总是暴露于显著水平的谷氨酸中，且在传递过程中谷氨酸水平呈梯度变化。
Synapses of glutamatergic mossy fibers (MFs) onto cerebellar unipolar brush cells (UBCs) generate slow excitatory (ON) or inhibitory (OFF) postsynaptic responses dependent on the complement of glutamate receptors expressed on the UBC’s large dendritic brush. Using mouse brain slice recording and computational modeling of synaptic transmission, we found that substantial glutamate is maintained in the UBC synaptic cleft, sufficient to modify spontaneous firing in OFF UBCs and tonically desensitize AMPARs of ON UBCs. The source of this ambient glutamate was spontaneous, spike-independent exocytosis from the MF terminal, and its level was dependent on activity of glutamate transporters EAAT1–2. Increasing levels of ambient glutamate shifted the polarity of evoked synaptic responses in ON UBCs and altered the phase of responses to in vivo-like synaptic activity. Unlike classical fast synapses, receptors at the UBC synapse are virtually always exposed to a significant level of glutamate, which varies in a graded manner during transmission.