Associative Learning Group, Department of Experimental Medical Science, Lund University, BMCF10, 22184, Lund, Sweden.
Sci Rep. 2020 Sep 24;10(1):15654. doi: 10.1038/s41598-020-72581-8.
In the eyeblink conditioning paradigm, cerebellar Purkinje cells learn to respond to the conditional stimulus with an adaptively timed pause in its spontaneous firing. Evidence suggests that the pause is elicited by glutamate released from parallel fibers and acting on metabotropic receptors (mGluR7) which initiates a delayed-onset suppression of firing. We suggested that G protein activation of hyperpolarizing K3 channels (or 'GIRK', G protein-coupled inwardly-rectifying K channels) could be part of such a mechanism. Application of the K3 antagonist Tertiapin-LQ locally in the superficial layers of the cerebellar cortex in decerebrate ferrets suppressed normal performance of Purkinje cell pause responses to the conditional stimulus. Importantly, there was no detectable effect on spontaneous firing. These findings suggest that intact functioning of K3 channels in the cerebellar cortex is required for normal conditioned Purkinje cell responses.
在眨眼条件反射范式中，小脑浦肯野细胞学会对条件刺激做出反应，即在其自发放电时适应性地暂停。有证据表明，这种暂停是由来自平行纤维的谷氨酸释放引起的，作用于代谢型受体（mGluR7），从而引发延迟发作的放电抑制。我们认为，G 蛋白激活超极化 K3 通道（或“GIRK”，G 蛋白偶联内向整流 K 通道）可能是这种机制的一部分。在去大脑的雪貂的小脑皮质浅层局部应用 K3 拮抗剂 Tertiapin-LQ 抑制了浦肯野细胞对条件刺激的暂停反应的正常表现。重要的是，对自发放电没有可检测到的影响。这些发现表明，小脑皮质中 K3 通道的完整功能对于正常的条件反射浦肯野细胞反应是必需的。
