Properties of 4Hz stimulation-induced parallel fiber-Purkinje cell presynaptic long-term plasticity in mouse cerebellar cortex in vivo
Properties of 4Hz stimulation-induced parallel fiber-Purkinje cell presynaptic long-term plasticity in mouse cerebellar cortex in vivo
复制标题
体内小鼠小脑皮质4Hz刺激诱导平行纤维浦肯野细胞突触前长期可塑性的特性
DOI：
10.1111/ejn.12559
复制
发表时间：
2014-05-01
影响因子：
3.4
通讯作者：
Qiu, De-Lai
中科院分区：
文献类型：
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作者：
Chu, Chun-Ping;Zhao, Guo-Yan;Qiu, De-Lai
小脑平行纤维-浦肯野细胞(PF-PC)的长期突触可塑性对小脑神经元回路的形成和稳定具有重要意义，并为运动学习和记忆提供底物。我们先前在体外报道了小脑PF-PC突触的突触前长时程增强(LTP)和长时程抑制(LTD)。然而，小脑PF-PC突触可塑性在体内小脑皮质中的表达及其机制尚不清楚。本研究采用乌拉坦麻醉小鼠在体膜片钳全细胞记录技术和药理学方法，研究了4 Hz刺激诱发的Pf-PC突触前长时程可塑性的特性。结果表明，4 HzPf刺激可在正常小鼠小脑皮质诱导突触前LTD的Pf-PC突触传递。突触前LTD可被N-甲基-D-天冬氨酸受体拮抗剂D-氨基膦戊酸或代谢型谷氨酸受体拮抗剂JNJ16259685减弱，并可被D-氨基膦戊酸和JNJ16259685联合应用而增强。阻断大麻素1型受体的活性可使PF-PC LTD消失，并显示突触前的PF-PC LTP。这些结果表明，内源性大麻素和一氧化氮合酶都参与了4 Hz刺激诱导的PF-PC突触前可塑性，但依赖内源性大麻素的PF-PC突触前LTP掩盖了乌拉坦麻醉小鼠小脑皮质中一氧化氮介导的PF-PC突触前LTP。
Cerebellar parallel fiber-Purkinje cell (PF-PC) long-term synaptic plasticity is important for the formation and stability of cerebellar neuronal circuits, and provides substrates for motor learning and memory. We previously reported both presynaptic long-term potentiation (LTP) and long-term depression (LTD) in cerebellar PF-PC synapses in vitro. However, the expression and mechanisms of cerebellar PF-PC synaptic plasticity in the cerebellar cortex in vivo are poorly understood. In the present study, we studied the properties of 4Hz stimulation-induced PF-PC presynaptic long-term plasticity using in vivo the whole-cell patch-clamp recording technique and pharmacological methods in urethane-anesthetised mice. Our results demonstrated that 4Hz PF stimulation induced presynaptic LTD of PF-PC synaptic transmission in the intact cerebellar cortex in living mice. The PF-PC presynaptic LTD was attenuated by either the N-methyl-D-aspartate receptor antagonist, D-aminophosphonovaleric acid, or the group 1 metabotropic glutamate receptor antagonist, JNJ16259685, and was abolished by combined D-aminophosphonovaleric acid and JNJ16259685, but enhanced by inhibition of nitric oxide synthase. Blockade of cannabinoid type 1 receptor activity abolished the PF-PC LTD and revealed a presynaptic PF-PC LTP. These data indicate that both endocannabinoids and nitric oxide synthase are involved in the 4Hz stimulation-induced PF-PC presynaptic plasticity, but the endocannabinoid-dependent PF-PC presynaptic LTD masked the nitric oxide-mediated PF-PC presynaptic LTP in the cerebellar cortex in urethane-anesthetised mice.