Potentiation of mossy fiber EPSCs in the cerebellar nuclei by NMDA receptor activation followed by postinhibitory rebound current
Potentiation of mossy fiber EPSCs in the cerebellar nuclei by NMDA receptor activation followed by postinhibitory rebound current
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DOI：
10.1016/j.neuron.2006.05.021
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发表时间：
2006-07-06
期刊：
影响因子：
16.2
通讯作者：
Raman, Indira M.
中科院分区：
文献类型：
--
作者：
Pugh, Jason R.;Raman, Indira M.
行为和计算研究预测，突触可塑性的兴奋性苔藓纤维输入小脑核神经元所需的联想学习，但标准的强直协议未能加强小鼠小脑切片中的核细胞EPSC。除非受到浦肯野神经元的强烈抑制，否则核神经元会自发地激发动作电位，这增加了这些细胞中的可塑性触发信号与经典的赫布突触不同的可能性。基于对延迟眼睑调节过程中神经元活动的预测，我们开发了由高频苔藓纤维刺激和突触后超极化组成的准生理诱导方案。强大的，NMDA受体依赖性增强的核细胞EPSCs发生的协议，包括150-250毫秒的超极化，苔藓纤维刺激之前的抑制后反弹去极化。苔藓纤维刺激增强EPSCs，即使突触后尖峰被阻止电压钳，只要诱发反弹电流。这些数据表明，浦肯野细胞抑制指导小脑核兴奋性突触的加强。
Behavioral and computational studies predict that synaptic plasticity of excitatory mossy fiber inputs to cerebellar nuclear neurons is required for associative learning, but standard tetanization protocols fail to potentiate nuclear cell EPSCs in mouse cerebellar slices. Nuclear neurons fire action potentials spontaneously unless strongly inhibited by Purkinje neurons, raising the possibility that plasticity-triggering signals in these cells differ from those at classical Hebbian synapses. Based on predictions of neuronal activity during delay eyelid conditioning, we developed quasi-physiological induction protocols consisting of high-frequency mossy fiber stimulation and postsynaptic hyperpolarization. Robust, NMDA receptor-dependent potentiation of nuclear cell EPSCs occurred with protocols including a 150-250 ms hyperpolarization in which mossy fiber stimulation preceded a postinhibitory rebound depolarization. Mossy fiber stimulation potentiated EPSCs even when postsynaptic spiking was prevented by voltage-clamp, as long as rebound current was evoked. These data suggest that Purkinje cell inhibition guides the strengthening of excitatory synapses in the cerebellar nuclei.