Distinct Roles of Gαqand Gα11for Purkinje Cell Signaling and Motor Behavior

Abstract

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_qfamily, namely G_qand G₁₁. Althoughin vitrocoexpression of mGluR1 with either Gα₁₁or Gα_qproduces equally well functioning signaling cascades, Gα_q- and Gα₁₁-deficient mice exhibit distinct alterations in motor coordination. By using whole-cell recordings and Ca²⁺imaging in Purkinje cells, we show that Gα_qis required for mGluR-dependent synaptic transmission and for long-term depression (LTD). Gα₁₁has 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 Gα_qversus Gα₁₁. Our findings suggest an expression level-dependent action of Gα_qand Gα₁₁for Purkinje cell signaling and assign specific roles of these two G_qisoforms for motor coordination.