Hypocretin (orexin) neuron activity in the rat during sleep and waking behavior (long)

The loss of hypocretin (orexin) neurons is responsible for narcolepsy (see the top left box on the home page). Because the loss of these neurons causes narcolepsy, it has been assumed that they are active whenever animals are awake. This is incorrect. They are relatively inactive during sleep, but in waking they are not continuously active and are not simply related to EEG arousal. Rather they are maximally active during eating, exploration and grooming, i.e. pleasant states. They are inactive when the rat is recoiling from the first piece of chicken he has ever seen, but when he decides to eat the chicken the neuron becomes very active. This pleasure related activation is consistent with our work showing that the activity of these neurons is linked to opioid addiction (left side of home page (work by Thannickal et al., 2018 and MacGregor et al., 2023 in the lab, and others). In Blouin et al., 2013, also in the left column on the home page, we show that hypocretin release in humans is maximal during pleasure, including positive social interactions, but is minimal in pain, even if the pain is highly arousing, consistent with our neuronal recordings of hypocretin neurons in rats, release of hypocretin in dogs and humans and with the relation of these neurons to addiction.