Regulation of synaptic plasticity and learning by cross-talk of G protein-coupled receptors

Our electrophysiological analyses in cultured mouse cerebellar Purkinje cells suggest that ligand-activated adenosine A1 receptor (A1R) impedes cerebellar long-term depression (LTD) by decreasing the glutamate-sensitivity of type-1 metabotropic glutamate receptor (mGluR1), a key trigger of induction of cerebellar LTD. Our in-vivo behavioral analyses showed that activation of B-type gamma-amino butyric acid receptor (GABAbR) facilitated cerebellar LTD-dependent motor learning. These findings suggest that in response to neuromodulators in the cereberospinal fluid, A1R and GABAbR modulate mGluR1 and thereby regulate induction of synaptic plasticity and learning.