ABSTRACT
The discovery of the hypocretins [Hcrt; (1)] [also known as the orexins (2)], the receptors for these peptides (2) and the subsequent links of defects in this neuropeptide system to narcolepsy or narcoleptic-like syndromes in dogs (3), mice (4) and humans (5,6) has raised the prospect of new therapeutic avenues for narcoleptic patients. One of the earliest neuroanatomical studies of the Hcrt system indicated that the axonal projections of these cells terminated in brain regions that have been classically implicated in arousal state control (7). These anatomical relations of the Hcrt cells, coupled with pathology of wakefulness that results from disruption of the Hcrt system, led us to propose a model in which the Hcrt neurons played a central role in the control of behavioral state (8). A key component of this model was a putative role for inhibitory GABAergic input to the Hcrt cells in mediating the transition from wakefulness to slow wave sleep. This feature of our model has been retained in other recently proposed models (9,10).
