Dopaminergic cAMP signaling in mouse olfactory bulb astrocytes

Abstract

Cyclic AMP (cAMP) is an important second messenger in virtually all animal cell types, including astrocytes. In the brain, it modulates energy metabolism, development and synaptic plasticity. Dopamine receptors are G protein-coupled receptors that affect cAMP production by adenylyl cyclases. They are divided into two subgroups, D1-like receptors linked to G_s proteins stimulating cAMP production and D2-like receptors linked to G_i/o proteins inhibiting cAMP production. In the present study, we investigated the effect of dopamine receptor activation on cAMP dynamics in astrocytes of the mouse olfactory bulb, the brain region with the largest population of dopaminergic neurons. Using the genetically encoded cAMP sensor Flamindo2 we visualized changes in the cytosolic cAMP concentration and showed that dopamine application results in a transient increase in cAMP. This cAMP increase could be mimicked by the D1-like receptor agonist A 68930 and was inhibited by the D1-like receptor antagonist SCH 23390, whereas D2-like receptor ligands had no effect on the astrocytic cAMP concentration. Thus, olfactory bulb astrocytes express D1-like receptors that are linked to cAMP production.

Keywords: Astrocytes; Cyclic adenosine monophosphate; D1 receptor; Dopamine; Olfactory bulb.