Muscarinic Receptor Modulation of the Cerebellar Interpositus Nucleus In Vitro.

Muscarinic Receptor Modulation of the Cerebellar Interpositus Nucleus In Vitro.
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DOI:
10.1007/s11064-018-2613-9
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发表时间:
2019-03
影响因子:
4.4
通讯作者:
Bashir ZI
Bashir ZI
中科院分区:
医学3区
文献类型:
--
作者:
Pickford J;Apps R;Bashir ZI

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小脑如何执行其功能尚不清楚,即使它在运动控制中的既定角色也是如此。特别是,很少有人知道小脑核(CN)如何整合其突触和神经调节输入,以产生小脑输出。CN神经元接受来自浦肯野细胞的抑制性输入、来自苔藓纤维和攀缘纤维侧支的兴奋性输入以及各种神经调节性输入,包括胆碱能输入。在这项研究中,我们测试了如何激活乙酰胆碱受体调制放电率,内在属性和突触传递的CN。使用在体外全细胞膜片钳记录从神经元的间位核,乙酰胆碱受体激动剂卡巴胆碱被证明诱导短期增加放电率,增加保持电流和降低输入电阻的间位CN神经元。卡巴胆碱还诱导诱发抑制性突触后电流的长期抑郁症和诱发兴奋性突触后电流的短期抑郁症。所有的影响都被证明是依赖于毒蕈碱乙酰胆碱受体激活。总体而言,本研究已确定毒蕈碱受体活化作为CN活性的调节剂。
How the cerebellum carries out its functions is not clear, even for its established roles in motor control. In particular, little is known about how the cerebellar nuclei (CN) integrate their synaptic and neuromodulatory inputs to generate cerebellar output. CN neurons receive inhibitory inputs from Purkinje cells, excitatory inputs from mossy fibre and climbing fibre collaterals, as well as a variety of neuromodulatory inputs, including cholinergic inputs. In this study we tested how activation of acetylcholine receptors modulated firing rate, intrinsic properties and synaptic transmission in the CN. Using in vitro whole-cell patch clamp recordings from neurons in the interpositus nucleus, the acetylcholine receptor agonist carbachol was shown to induce a short-term increase in firing rate, increase holding current and decrease input resistance of interpositus CN neurons. Carbachol also induced long-term depression of evoked inhibitory postsynaptic currents and a short-term depression of evoked excitatory postsynaptic currents. All effects were shown to be dependent upon muscarinic acetylcholine receptor activation. Overall, the present study has identified muscarinic receptor activation as a modulator of CN activity.
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