Activity-dependent plasticity of presynaptic GABA(B) receptors at parallel fiber synapses.
Activity-dependent plasticity of presynaptic GABA(B) receptors at parallel fiber synapses.
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DOI：
10.1002/syn.22027
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发表时间：
2018-05
期刊：
影响因子：
--
通讯作者：
Pugh JR
中科院分区：
文献类型：
--
作者：
Orts-Del'Immagine A;Pugh JR
小脑中的平行纤维突触表达广泛的突触前受体。然而，突触前受体在单个平行纤维突触的表达是相当异质性的，这表明生理机制调节突触前受体的表达。我们研究了幼年小鼠急性小脑切片中平行纤维-星状细胞突触的突触前GABAB受体的变化。GABAB受体介导的兴奋性突触后电流（EPSC）抑制在这些突触中是显著不同的，其中在一些突触中的递质释放被抑制>50%，而在其他突触中很少或没有抑制。GABAB受体介导的抑制显着减少4 Hz平行纤维刺激后，但不是在其他频率的刺激后。GABAB受体介导的抑制作用的减少被毛喉素的浴应用复制，并通过PKA抑制剂的应用被阻断，这表明腺苷酸环化酶和PKA的激活是必需的。免疫标记的GABAB 2亚基的细胞外结构域显示减少暴露于毛喉素后的分子层中的表面表达。GABAB受体介导的抑制动作电位诱发的钙瞬变平行纤维静脉曲张也减少后浴应用毛喉素，确认突触前受体是负责减少EPSC抑制。这些数据表明，突触前GABAB受体的表达可以是突触的可塑性，这可能会补充其他形式的突触可塑性。这为以前主要局限于突触后受体的新型受体可塑性打开了大门。
Parallel fiber synapses in the cerebellum express a wide range of presynaptic receptors. However, presynaptic receptor expression at individual parallel fiber synapses is quite heterogeneous, suggesting physiological mechanisms regulate presynaptic receptor expression. We investigated changes in presynaptic GABAB receptors at parallel fiber-stellate cell synapses in acute cerebellar slices from juvenile mice. GABAB receptor-mediated inhibition of excitatory postsynaptic currents (EPSCs) is remarkably diverse at these synapses, with transmitter release at some synapses inhibited by >50% and little or no inhibition at others. GABAB receptor-mediated inhibition was significantly reduced following 4 Hz parallel fiber stimulation but not after stimulation at other frequencies. The reduction in GABAB receptor-mediated inhibition was replicated by bath application of forskolin and blocked by application of a PKA inhibitor, suggesting activation of adenylyl cyclase and PKA are required. Immunolabeling for an extracellular domain of the GABAB2 subunit revealed reduced surface expression in the molecular layer after exposure to forskolin. GABAB receptor-mediated inhibition of action potential evoked calcium transients in parallel fiber varicosities was also reduced following bath application of forskolin, confirming presynaptic receptors are responsible for the reduced EPSC inhibition. These data demonstrate that presynaptic GABAB receptor expression can be a plastic property of synapses, which may compliment other forms of synaptic plasticity. This opens the door to novel forms of receptor plasticity previously confined primarily to postsynaptic receptors.
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影响因子：
5.8
作者：
Adelfinger, Lisa;Turecek, Rostislav;Ivankova, Klara;Jensen, Anders A.;Moss, Stephen J.;Gassmann, Martin;Bettler, Bernhard
通讯作者：
Bettler, Bernhard
影响因子：
5.3
作者：
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通讯作者：
Augustine, George J.
影响因子：
16.2
作者：
Ehlers, MD
通讯作者：
Ehlers, MD
影响因子：
8.8
作者：
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通讯作者：
Casado, Mariano
影响因子：
4.7
作者：
Cimarosti, Helena;Kantamneni, Sriharsha;Henley, Jeremy M.
通讯作者：
Henley, Jeremy M.