Metabotropic glutamate receptors 1 and 5 differentially regulate bulbar dopaminergic cell function

Effects of activation of metabotropic glutamatergic receptors (mGluR) were investigated in mouse dopaminergic olfactory bulb neurons. After blockage of ionotropic receptors, focal application of glutamate or of group I/II mGluR agonist t-ACPD resulted in a depolarization, paralleled by an inward current in voltage-clamp conditions. The Group I agonist DHPG induced a depolarization, which could be largely blocked by mGluR1 antagonists. The DHPG action i) was prevented by buffering intracellular Ca2+ with BAPTA and by a phospholipase C inhibitor; ii) was not affected by the block of Ca2+ entry, and iii) was blocked by inhibitors of the Na+/Ca2+ exchanger. These observations were interpreted as a mGluR1-mediated intracellular Ca2+ release, followed by the activation of an electrogenic Na+/Ca2+ exchanger. The mGluR5 agonist CHPG induced a hyperpolarization of membrane potential, resulting in a decrease of the spontaneous firing frequency. CHPG induced i) a decrease in membrane resistance; ii) an increase in the action potential repolarization rate, and iii) an increase in the amplitude of the afterhyperpolarization. This was interpreted as a mGluR5-mediated opening of a K+ conductance. These data suggest that mGluR1 and mGluR5 play different and non-overlapping roles in the regulation of the excitability of bulbar dopaminergic neurons.

Research highlights► mGluR were investigated in mouse dopaminergic olfactory bulb neurons. ► mGluR1 mediates the activation of an electrogenic Na+/Ca2+ exchanger. ► mGluR5 mediates the opening of a K+ conductance. ► mGluR1 and mGluR5 play different and non-overlapping roles.