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

Abstract

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 (GABAg), 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. Show more