Dopamine receptor subtypes modulate olfactory bulb gamma-aminobutyric acidtype A receptors

The gamma-aminobutyric acid type A (GABA(A)) receptor is the predominant Cl - channel protein mediating inhibition in the olfactory bulb and elsewhere in the mammalian brain. The olfactory bulb is rich in neurons containing bo th GABA and dopamine. Dopamine D1 and D2 receptors are also highly expresse d in this brain region with a distinct and complementary distribution patte rn. This distribution suggests that dopamine may control the GABAergic inhi bitory processing of odor signals, possibly via different signal-transducti on mechanisms. We have observed that GABA(A) receptors in the rat olfactory bulb are differentially modulated by dopamine in a cell-specific manner. D opamine reduced the currents through GABA-gated Cl- channels in the interne urons, presumably granule cells. This action was mediated via D1 receptors and involved phosphorylation of GABA(A) receptors by protein kinase A. Enha ncement of GABA responses via activation of D2 dopamine receptors and phosp horylation of GABA(A) receptors by protein kinase C was observed in mitral/ tufted cells. Decreasing or increasing the binding affinity for GABA appear s to underlie the modulatory effects of dopamine via distinct receptor subt ypes. This dual action of dopamine on inhibitory GABA(A) receptor function in the rat olfactory bulb could be instrumental in odor detection and discr imination, olfactory learning, and ultimately odotopic memory formation.