GABA_B receptor-mediated modulation of glutamate signaling in cerebellar Purkinje cells

Since Purkinje cells are the sole output neurons of the cerebellar cortex, the postsynaptic integration of excitatory and inhibitory synaptic inputs in this cell type is a pivotal step for cerebellar motor information processing. In Purkinje cells, G i/o protein-coupled B-type γ-aminobutyric acid receptor (GABA B R) is expressed at the annuli of the dendritic spines that are innervated by the glutamatergic terminals of parallel fibers. The subcellular localization of GABA B R suggests the possibility of postsynaptic interplay between GABA B R and glutamate signaling. It has recently been demonstrated that GABA B R indeed modulates α amino-3-hydroxy-5-methyl-4-isoxalone propionate-type ionotropic glutamate receptor (AMPAR)-mediated and type-1 metabotropic glutamate receptor (mGluR1)-mediated signaling. Interestingly, GABA B R exerts modulatory actions not only via the classical G i/o protein-dependent signaling cascade but also via a G i/o protein-independent interaction between GABA B R and mGluR1. In this review, we compare the physiological nature, underlying mechanisms, and possible functional significance of these modulatory actions of GABA B R.