Influence of ambient neuromodulators on learning through hetero-GPCR interplay

在小脑浦肯野细胞中，B型γ-氨基丁酸受体（GABAbR）和1型腺苷受体（A1 R）被认为是调节1型代谢型谷氨酸受体（mGluR 1）的细胞内信号触发诱导小脑长期抑郁症（LTD）。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OKR适应，这是一种小脑LTD依赖性学习。此外，使用体外制剂，我们发现A1 R通过其C-末端与mGluR 1相互作用，并且A1 R活化通过以G蛋白非依赖性方式降低mGluR 1的配体敏感性来抑制浦肯野细胞的谷氨酸反应性的LTD。异源G蛋白偶联受体的相互作用可能影响中枢突触可塑性和学习。

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.