Influence of ambient neuromodulators on learning through hetero-GPCR interplay

在小脑Purkinje细胞中，B型γ-氨基丁酸受体(GABAbR)和1型腺苷受体(A1R)被认为调节1型代谢性谷氨酸受体(MGluR1)，其细胞内信号触发小脑长期抑郁(LTD)的诱导。使用基于机器视觉的视动反射(OKR)测量系统，我们发现在小鼠中，小脑注射GABAbR激动剂促进了OKR适应，这是一种小脑LTD依赖的学习。此外，在体外实验中，我们发现A1R通过其C末端与mGluR1相互作用，并且A1R的激活通过非依赖G蛋白的方式降低mGluR1‘S配体的敏感性来抑制浦肯野细胞对谷氨酸反应的LTD。异型G蛋白偶联受体的相互作用可能影响中枢突触的可塑性和学习。

In cerebellar Purkinje cells, B-type gamma-aminobutyric acid receptor (GABAbR) and type-1 adenosine receptor (A1R) are suggested to modulate type-1 metabotropic glutamate receptor (mGluR1) whose intracellular signaling triggers induction of cerebellar long-term depression (LTD). Using a machine vision-based optokinetic reflex (OKR) measuring system, we found that in mice, cerebellar injection of a GABAbR agonist facilitated OKR adaptation, a cerebellar LTD-dependent learning. Moreover, using in-vitro preparations, we found that A1R interacted with mGluR1 via its C-terminus and that A1R activation suppressed the LTD of Purkinje cell's glutamate-responsiveness by lowering mGluR1's ligand-sensitivity in a G protein-independent manner. The hetero-G protein-coupled receptor interplay may influence central synaptic plasticity and learning.