Distinct roles of Gαq and Gα11 for Purkinje cell signaling and motor behavior

G-protein-coupled metabotropic glutamate group I receptors (mGluR1s) mediate synaptic transmission and plasticity in Purkinje cells and, therefore, critically determine cerebellar motor control and learning. Purkinje cells express two members of the G-protein G(q) family, namely G(q) and G(11). Although in vitro coexpression of mGluR1 with either Galpha(11) or Galpha(q) produces equally well functioning signaling cascades, Galpha(q)- and Galpha(11)-deficient mice exhibit distinct alterations in motor coordination. By using whole-cell recordings and Ca2+ imaging in Purkinje cells, we show that Galpha(q) is required for mGluR-dependent synaptic transmission and for long-term depression (LTD). Galpha(11) has no detectable contribution for synaptic transmission but also contributes to LTD. Quantitative single-cell RT-PCR analyses in Purkinje cells demonstrate a more than 10-fold stronger expression of Galpha(q) versus Galpha(11). Our findings suggest an expression level-dependent action of Galpha(q) and Galpha(11) for Purkinje cell signaling and assign specific roles of these two G(q) isoforms for motor coordination.