α-adrenoceptive dual modulation of inhibitory GABAergic inputs to Purkinje cells in the mouse cerebellum
α-adrenoceptive dual modulation of inhibitory GABAergic inputs to Purkinje cells in the mouse cerebellum
复制标题
DOI：
10.1152/jn.00711.2005
复制
发表时间：
2006-02-01
影响因子：
2.5
通讯作者：
Obata, K
中科院分区：
文献类型：
--
作者：
Hirono, M;Obata, K
去甲肾上腺素 (NA) 调节中枢神经系统各个部位的突触传递。在小脑皮质中，多项研究表明 NA 通过 β-肾上腺素受体和环 AMP 依赖性途径增强抑制性突触传递。然而，β-肾上腺素受体激活对小脑抑制性神经传递的影响尚未完全阐明。因此，我们研究了 α(1) 或 α(2)-肾上腺素受体激动剂对小鼠浦肯野细胞 (PC) 记录的抑制性突触后电流 (IPSC) 的影响。我们发现非选择性α-肾上腺素受体激动剂6-氟去甲肾上腺素增加了自发IPSC（s\IPSC）的频率和幅度。这种增强作用主要是由选择性 α(1)-肾上腺素受体激动剂去氧肾上腺素 (PE) 模仿的。 PE 还增强了诱发 IPSC (eIPSC) 的振幅并增加了微型 IPSC (mIPSC) 的频率，但没有增加其振幅。此外，PE 降低了 eIPSC 的配对脉冲比，并且没有改变 PC 中的γ-氨基丁酸（GABA）受体敏感性。相反，选择性α(2)-肾上腺素受体激动剂可乐定显着降低了sIPSC的频率和幅度。 eIPSC 和 mIPSC 均不受可乐定影响。此外，突触前细胞附着记录表明，PE 增强了 GABA 能中间神经元的自发活性，但可乐定降低了 GABA 能中间神经元的自发活性。这些结果表明，NA 增强了在突触前末梢和体树突结构域中表达的 α(1)-肾上腺素受体的抑制性神经递质释放，而 NA 通过在突触前体树突结构域中表达的 α(2)-肾上腺素受体抑制了中间神经元的兴奋性。因此，小脑α-肾上腺素受体在从中间神经元到PC的GABA能输入的突触前双重调节中发挥作用，从而为小脑皮质中信息流的微调提供了可能的机制。
Noradrenaline (NA) modulates synaptic transmission in various sites of the CNS. In the cerebellar cortex, several studies have revealed that NA enhances inhibitory synaptic transmission by beta-adrenoceptor- and cyclic AMP-dependent pathways. However, the effects of beta-adrenoceptor activation on cerebellar inhibitory neurotransmission have not yet been fully elucidated. Therefore we investigated the effects of the alpha(1) or alpha(2)-adrenoceptor agonist on inhibitory postsynaptic currents (IPSCs) recorded from mouse Purkinje cells (PCs). We found that the nonselective alpha-adrenoceptor agonist 6-fluoro-norepinephrine increased both the frequency and amplitude of spontaneous IPSCs (s\IPSCs). This enhancement was mostly mimicked by the selective alpha(1)-adrenoceptor agonist phenylephrine (PE). PE also enhanced the amplitude of evoked IPSCs (eIPSCs) and increased the frequency but not the amplitude of miniature IPSCs (mIPSCs). Moreover, PE decreased the paired-pulse ratio of eIPSCs and did not change gamma-aminobutyric acid (GABA) receptor sensitivity in PCs. Conversely, the selective alpha(2)-adrenoceptor agonist clonidine significantly reduced both the frequency and the amplitude of sIPSCs. Neither eIPSCs nor mIPSCs were affected by clonidine. Furthermore, presynaptic cell-attached recordings showed that spontaneous activity of GABAergic interneurons was enhanced by PE but reduced by clonidine. These results suggest that NA enhances inhibitory neurotransmitter release by alpha(1)-adrenoceptors, which are expressed in presynaptic terminals and somatodendritic domains, whereas NA suppresses the excitability of interneurons by alpha(2)-adrenoceptors, which are expressed in presynaptic somatodendritic domains. Thus cerebellar alpha-adrenoceptors play roles in a presynaptic dual modulation of GABAergic inputs from interneurons to PCs, thereby providing a likely mechanism for the fine-tuning of information flow in the cerebellar cortex.