Corticotrophin-Releasing Factor Modulates Cerebellar Purkinje Cells Simple Spike Activity in Vivo in Mice.
Corticotrophin-Releasing Factor Modulates Cerebellar Purkinje Cells Simple Spike Activity in Vivo in Mice.
复制标题
促肾上腺皮质激素释放因子调节小鼠体内小脑浦肯野细胞简单尖峰活动。
DOI：
10.3389/fncel.2018.00184
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发表时间：
2018
影响因子：
5.3
通讯作者：
Qiu DL
中科院分区：
文献类型：
--
作者：
Wang HW;Zhao JT;Li BX;Su SS;Bing YH;Chu CP;Wang WM;Li YZ;Qiu DL
促肾上腺皮质激素释放因子（CRF）是一种主要的神经调质，在应激反应中通过CRF受体调节小脑神经元的活动。在小脑皮质，CRF剂量依赖性地增加浦肯野细胞（PC）的简单锋电位（SS）放电率，而这一突触机制尚不清楚。本文采用在体电生理记录和药理学方法研究了CRF对麻醉小鼠小脑PC自发SS活动的影响。从PC的细胞贴附记录表明，在小脑皮质分子层的CRF的微应用诱导的剂量依赖性增加SS放电率的GABAA受体活性的情况下。CRF诱导的SS放电频率增加可被非选择性CRF受体拮抗剂α-螺旋CRF-（9-14）完全阻断。然而，应用选择性CRF-R1拮抗剂BMS-763534（BMS，200 nM）或选择性CRF-R2拮抗剂antisauvagine-30（200 nM）显著减弱，但未能消除CRF诱导的PC SS放电率增加。在体内全细胞膜片钳记录从PC显示，CRF的分子层应用显着增加的频率，但不是振幅，微型突触后电流（mEPSC）。CRF诱导的mEPSC频率增加被CRF-R2拮抗剂以及蛋白激酶A（PKA）抑制剂消除。这些结果提示CRF通过PKA信号通路作用于突触前小脑PC的CRF-R2，导致谷氨酸释放增加，从而参与了在体小脑PC输出的调节。
Corticotropin-releasing factor (CRF) is a major neuromodulator that modulates cerebellar neuronal activity via CRF receptors during stress responses. In the cerebellar cortex, CRF dose-dependently increases the simple spike (SS) firing rate of Purkinje cells (PCs), while the synaptic mechanisms of this are still unclear. We here investigated the effect of CRF on the spontaneous SS activity of cerebellar PCs in urethane-anesthetized mice by in vivo electrophysiological recording and pharmacological methods. Cell-attached recordings from PCs showed that micro-application of CRF in cerebellar cortical molecular layer induced a dose-dependent increase in SS firing rate in the absence of GABAA receptor activity. The CRF-induced increase in SS firing rate was completely blocked by a nonselective CRF receptor antagonist, α-helical CRF-(9–14). Nevertheless, application of either a selective CRF-R1 antagonist, BMS-763534 (BMS, 200 nM) or a selective CRF-R2 antagonist, antisauvagine-30 (200 nM) significantly attenuated, but failed to abolished the CRF-induced increase in PCs SS firing rate. In vivo whole-cell patch-clamp recordings from PCs showed that molecular layer application of CRF significantly increased the frequency, but not amplitude, of miniature postsynaptic currents (mEPSCs). The CRF-induced increase in the frequency of mEPSCs was abolished by a CRF-R2 antagonist, as well as protein kinase A (PKA) inhibitors. These results suggested that CRF acted on presynaptic CRF-R2 of cerebellar PCs resulting in an increase of glutamate release through PKA signaling pathway, which contributed to modulation of the cerebellar PCs outputs in Vivo in mice.
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影响因子：
3.2
作者：
LUO, X;KISS, A;AGUILERA, G
通讯作者：
AGUILERA, G
影响因子：
16.2
作者：
Nagy, G;Reim, K;Sorensen, JB
通讯作者：
Sorensen, JB
影响因子：
3.3
作者：
BISHOP, GA
通讯作者：
BISHOP, GA
影响因子：
5.3
作者：
King, JS;Bishop, GA
通讯作者：
Bishop, GA
影响因子：
5.2
作者：
Hauger RL;Risbrough V;Oakley RH;Olivares-Reyes JA;Dautzenberg FM
通讯作者：
Dautzenberg FM