Influence of ambient neuromodulators on learning through hetero-GPCR interplay

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.