Explore the actions of different wake-promoting neurons in the brain, and learn about discoveries that show there’s more to know about sleep, wakefulness, and narcolepsy. Move the slider on the brain to the left and right to reveal neuronal pathways.
Histamine Neuronal Pathways1-6
Histamine is a neurotransmitter that plays an important role in stabilizing sleep-wake states.1
Histamine neurons in the TMN may be important for sustaining wakefulness for long periods during the day?7
BF, basal forebrain; DR, dorsal raphe; LC, locus coeruleus; LDT, laterodorsal tegmentum; LH, lateral hypothalamus; PPT, pedunculopontine tegmentum; TMN, tuberomammillary nucleus; VLPO, ventrolateral preoptic area; VTA, ventral tegmental area.
In an animal model of narcolepsy, reduced hypocretin activity throughout the brain led to fragmented wakefulness.7 When hypocretin activation was restored to only neurons in the TMN (the location of histamine neurons in the brain3), long bouts of wakefulness were significantly increased compared with controls and were similar to mice with normal hypocretin activity.7
In a mouse model, hypocretin activity was reduced by disrupting expression of the hypocretin receptor type 2 (HCRTR2). Local expression of HCRTR2 in the TMN was induced by microinjection of an adeno-associated viral vector (AAV) coding for Cre recombinase. Wakefulness was scored in 10-s epochs and bouts were characterized during the animals’ normal active period (7:00 PM to 7:00 AM).7