Schematic illustrating the connections from the hypocretin (Hcrt) cells (red) to some of the brain regions previously implicated in arousal state control. Aminergic nuclei are shown in gold; cholinergic regions are shown in blue. The Hcrt cells likely receive circadian input from the suprachiasmatic nuclei (SCN) shown in green, but it is not known whether such input is through a direct synaptic connection, through a multisynaptic pathway, or by a neurohumoral input. Synaptic outputs from the Hcrt cells to all regions illustrated are thought to be excitatory, based on the literature published to date. The connections between the aminergic nuclei in the brainstem and the cholinergic LDT are thought to be inhibitory. Degeneration of Hcrt neurons in human narcolepsy would result in loss of excitatory input to all these regions and, conceivably, a disruption of normal interaction between the aminergic and cholinergic cell groups. See Kilduff and Peyron (2000) for a full explanation of the model and its relevance to arousal state regulation. Based on other regulated physiological systems, it is likely that there are reciprocal connections from the brain regions illustrated to the Hcrt cells. Abbreviations: DRN, dorsal raphe nucleus; LC, locus coeruleus; LDT, laterodorsal tegmental nucleus; Nacc, nucleus accumbens; PPT, pedunculopontine nucleus; TMN, tuberomammillary nucleus; VTA, ventral tegmental area.
