Schmolesky M T, De Ruiter M M, De Zeeuw C I, Hansel C
Department of Neuroscience, Erasmus University Medical Centre, Postbus 2040, 3000 CA Rotterdam, The Netherlands.
Eur J Neurosci. 2007 Mar;25(5):1460-6. doi: 10.1111/j.1460-9568.2007.05409.x.
The climbing fibre (CF) input controls cerebellar Purkinje cell (PC) activity as well as synaptic plasticity at parallel fibre (PF)-PC synapses. Under high activity conditions, CFs release not only glutamate, but also the neuropeptide corticotropin-releasing factor (CRF). Brief periods of such high CF activity can lead to the induction of long-term depression (LTD) at CF-PC synapses. Thus, we have examined for the first time the role of CRF in regulating excitatory postsynaptic currents (EPSCs) and long-term plasticity at this synapse. Exogenous application of CRF alone transiently mimicked three aspects of CF-LTD, causing reductions in the CF-evoked excitatory postsynaptic current, complex spike second component and complex spike afterhyperpolarization. The complex spike first component is unaffected by CF-LTD induction and was similarly unaffected by CRF. Application of a CRF receptor antagonist reduced the expression amplitude and induction probability of CF-LTD monitored at the EPSC level. Collectively, these results suggest that under particular sensorimotor conditions, co-release of CRF from climbing fibres could down-regulate excitatory transmission and facilitate LTD induction at CF-PC synapses. Inhibition of either protein kinase C (PKC) or protein kinase A (PKA) attenuated the effects of CRF upon CF-EPSCs. We have previously shown that CF-LTD induction is PKC-dependent, and here demonstrate PKA-dependence as well. These results suggest that both the acute effects of CRF on CF-EPSCs as well as the facilitating effect of CRF on CF-LTD induction can be explained by a CRF-mediated recruitment of PKC and PKA.
攀缘纤维（CF）输入可控制小脑浦肯野细胞（PC）的活动以及平行纤维（PF）-PC突触处的突触可塑性。在高活动状态下，CF不仅释放谷氨酸，还释放神经肽促肾上腺皮质激素释放因子（CRF）。这种高CF活动的短暂时期可导致CF-PC突触处的长时程抑制（LTD）的诱导。因此，我们首次研究了CRF在调节该突触处兴奋性突触后电流（EPSC）和长时程可塑性中的作用。单独外源性应用CRF可短暂模拟CF-LTD的三个方面，导致CF诱发的兴奋性突触后电流、复合动作电位第二成分和复合动作电位超极化后电位降低。复合动作电位第一成分不受CF-LTD诱导的影响，同样也不受CRF的影响。应用CRF受体拮抗剂可降低在EPSC水平监测到的CF-LTD的表达幅度和诱导概率。总的来说，这些结果表明，在特定的感觉运动条件下，攀缘纤维共同释放CRF可下调兴奋性传递并促进CF-PC突触处的LTD诱导。抑制蛋白激酶C（PKC）或蛋白激酶A（PKA）可减弱CRF对CF-EPSC的作用。我们之前已经表明CF-LTD的诱导是PKC依赖性的，并且在此也证明了其PKA依赖性。这些结果表明，CRF对CF-EPSC的急性作用以及CRF对CF-LTD诱导的促进作用都可以通过CRF介导的PKC和PKA募集来解释。
