The histaminergic neurons of the tuberomamillary nucleus (TMN) in the posterior hypothalamus integrate and gate waking signals from multiple arousal centers; their silencing by GABA induces sleep (Sherin et al., 1996, 1998). Functional and structural features of the GABAA receptor in TMN neurons (Sergeeva et al., 2002, 2005) are important for the understanding of sleep regulation. It was previously hypothesized that general anesthetics may cause loss of consciousness through the inhibition of pathways that maintain cortical activation and behavioural arousal, as anesthetics acting at the GABAA receptor reduce cFos expression in TMN neurons (Nelson et al., 2002; Franks, 2008). Additional evidence was taken from the reduced modulation of sIPSCs by propofol in TMN neurons (Zecharia et al., 2009) of b3N265M mice (Jurd et al., 2003)with a point mutation causing substantial impairment of the "loss of righting reflex" by propofol. Using detailed pharmacological and single-cell RT-PCR analysis of GABAA receptor expression and function in TMN neurons with the help of the mutant b3N265M and 2F77I mice and a novel class of b1-selective GABAA receptor positive modulators we show a dominant role of b1 subunit-containing receptors in GABAergic inhibition and in the control of neuronal firing. Thus the posterior hypothalamus is a center for sleep-waking regulation that integrates immobilization by anesthetics but does not seem to serve as a primary target for anesthesia.