Emotionally salient situations usually trigger arousal along with autonomic and neuroendocrine reactions. To examine whether the extended amygdala plays a role in sleep/wakefulness regulation, we examined the effects of optogenetic and pharmacogenetic excitation of GABAergic neurons in the bed nucleus of the stria terminalis (GABA(BNST) neurons). Acute optogenetic excitation of these cells during non-rapid eye movement (NREM) sleep resulted in immediate state transition to wakefulness, while stimulation during rapid eye movement (REM) sleep showed no effect on sleep/wakefulness states in male mice. Anterograde tracing study suggested GABA(BNST) neurons send axonal projections to several brain regions implicated in arousal, including the preoptic area, lateral hypothalamus, periaqueductal gray, deep mesencephalic nucleus and parabrachial nucleus. A dual orexin receptor antagonist, DORA 22, did not affect the optogenetic transition from NREM sleep to wakefulness. Chemogenetic excitation of GABA(BNST) neurons evoked a sustained wakefulness state, but this arousal effect was markedly attenuated by DORA 22. These observations suggest that GABA(BNST) neurons play an important role in transition from NREM sleep to wakefulness without the function of orexin neurons, but prolonged excitation of these cells mobilizes the orexin system to sustain wakefulness.SIGNIFICANCE STATEMENTWe examined the role of the bed nucleus of the stria terminalis (BNST) in the regulation of wakefulness. Optogenetic excitation of GABAergic neurons in the BNST (GABA(BNST) neurons) during NREM sleep in mice resulted in immediate transition to a wakefulness state without function of orexins. Prolonged excitation of GABA(BNST) neurons by a chemogenetic method evoked a longer-lasting, sustained wakefulness state, which was abolished by pre-administration of a dual orexin receptor antagonist, DORA 22. This study revealed a role of the BNST GABAergic system in sleep-wakefulness control, especially in shifting animals' behavioral states from NREM sleep to wakefulness, and provides an important insight into the pathophysiology of insomnia and the role of orexin in arousal regulation.