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

The serotonin-1A [5-hydroxytryptamine 1A (5HT1A)] receptor is important for emotional and homeostatic processes in the central nervous system. In the hippocampus, the 5HT1A receptor couples to inhibitory Gi/o proteins to decrease pyramidal cell excitability. Here we investigate the 5HT1A receptor in a mouse deficient in the α-subunit of Gz protein (Gαz knock-out). Behavioural tests showed heightened anxiety and depression-like behaviour in the Gαz knock-out mice. Whole-cell recording in CA1 pyramidal neurons showed a significantly greater 5HT1A receptor-mediated potassium current in Gαz 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 Gαz knock-out mice. Other receptors linked to Gi/o proteins [γ-aminobutyric acid type B receptor (GABA_g), adenosine A1 and muscarinic acetylcholine receptors] were not affected in Gαz knock-out mice. These results suggest that the 5HT1A receptor may be linked to Gαz protein, as reported previously in cell culture but shown here in an intact neural network.