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D1- and D2-like dopamine receptors regulate signaling properties of group I metabotropic glutamate receptors in the rat globus pallidus


Dr P. Jeffrey Conn, as above.


Dopamine is essential to the proper functioning of basal ganglia (BG) because loss of dopaminergic input profoundly alters the activity of these nuclei. Experimental evidence suggests that multiple aspects of glutamatergic neurotransmission in the BG are altered with the loss of dopaminergic input. Using whole-cell patch-clamp recording in rat brain slices, we examined whether activity of dopamine receptors is necessary to maintain signaling properties of group I metabotropic glutamate receptor subtypes, mGluR1 and 5, in the rat globus pallidus (GP), one of the nuclei in the BG circuit. Dopaminergic depletion due to systemic treatment with reserpine caused a change in the signaling properties of group I mGluRs, where mGluR1 lost the ability to depolarize GP neurons, while mGluR5 gained such ability. Bath-application of dopamine or D1- and D2-like dopamine receptor agonists to slices from reserpinized rats partly reversed these effects and caused mGluR1 to gain back its ability to depolarize GP neurons. On the other hand, stimulation of either D1-like or D2-like dopamine receptors was sufficient to abolish the activating properties of mGluR5 acquired following reserpine treatment. Interestingly, inhibition of protein kinase A activity alone was sufficient to largely reverse plasticity in function of group I mGluRs that was induced by reserpine treatment. Our data reveal that specific roles of group I mGluRs in the GP depend on the activity of D1-like and D2-like dopamine receptors, further corroborating the importance of dopamine in maintaining proper glutamatergic neurotransmission in the BG.