Enhanced serotonin response in the hippocampus of Gαz protein knock-out mice

The serotonin-IA [5-hydroxytryptamine IA (5HTIA)] receptor is important for emotional and homeostatic processes in the central nervous system. In the hippocampus, the SHTIA receptor couples to inhibitory Gi/o proteins to decrease pyramidal cell excitability. Here we investigate the 5HTIA receptor in a mouse deficient in the a-subunit of Gz protein (G alpha z knock out). Behavioural tests showed heightened anxiety and depression-like behaviour in the Gaz knock-out mice. Whole-cell recording in CAI pyramidal neurons showed a significantly greater 5HTIA receptor-mediated potassium current in G alpha z knock out mice. The effect was independent of 5HT4 receptors as the slow after-hyperpolarization was unaffected and a slow depolarization was- absent in the G alpha z knock-out mice. Other receptors linked to Gi/o proteins [gamma-aminobutyric acid type B receptor (GABA(B)), adenosine AI and muscarinic acetylcholine receptors] were not affected in G alpha z knock out mice. These results suggest that the 5HTIA receptor may be linked to G alpha z protein, as reported previously in cell culture but shown here in an intact neural network. NeuroReport 16:921-925 (c) 2005 Lippincott Williams & Wilkins.