The lateral hypothalamus plays a large role in wakefulness, feeding behavior, learning, and sleep.
The lateral hypothalamus plays a large role in wakefulness, feeding behavior, learning, and sleep.
A common man’s wish is that he can sleep like a child. Indeed, in adults, the total hours of sleep and the quality of this sleep decrease with age. Older people are especially at risk of dysfunctional, fragmented sleep. Persistent decline in sleep quality and quantity can lead to a decline in mental and physical health, and to a shorter lifespan (Mander et al., neuron, 94, 19 (2017)).
Research has provided many clues as to what induces sleep in humans. The pineal gland, at night, releases the hormone melatonin which is involved in regulating the sleep-wake cycle. This has made it a popular supplement for overcoming insomnia, although its effectiveness beyond the short term remains a matter of debate.
However, our ‘awake’ state is much more complex, as it involves almost the entire brain. Perhaps this is why we are troubled by the often disrupted sleep of the elderly, where waking up repeatedly encroaches upon blissful sleep.
It is known that in older people with sleep disturbances, degeneration of nerve cells is observed in the brain centers involved in the coordination of voluntary movements. A recent study has added a new dimension to our knowledge (Lee et al., Science, 375, 2022). Studies point to the hypothalamus, which is located in the center of the brain and is almond-shaped and shaped. An area in this part of the brain, the lateral hypothalamus, plays a large role in wakefulness, feeding behavior, learning, and sleeping. From here there is a bunch of nerve cells that give their nerve endings to all those parts of the central nervous system that are associated with the state of stimulation. The chemical message released by these neurons is in the form of small proteins called hypocretins and also known as orexins (the two names come from two groups of scientists who independently discovered these neuropeptides in 1998). did).
Like all neurons, Hcrt/OX neurons have endings called synapses, which can be next to another neuron’s synapse or to a muscle cell. Electrical signals pass along the length of the neurons until they arrive at the synapse, where they are transiently transformed into chemical signals, which are passed across and trigger a response in the adjacent neuron. In neuroscience parlance, an excitatory signal will lead to the firing of the next neuron—the conduction of electrical signals to a synapse at the other end of that neuron. Inhibitory signals reduce the firing of an activated neuron. Hypocretin is excitatory, stimulating what reaches the neurons.
Hypocretin stimulates wakefulness, and with it, motivated behaviors such as seeking food or a mate, as well as responses to cold, nausea, or pain. Of the 86 billion neurons in the human brain, less than 20,000 produce hypocretin, but their effects are profound. Most of all, hypocretin is important for prolonged wakefulness. Injecting hypocretin directly into the cerebrospinal fluid (so that it is quickly delivered inside the brain) will keep you awake for several hours. And when you are sleeping the neurons that produce hypocretin are no longer active.
In experiments, food-deprived rats stay awake and engaged for a very long time in search of food. Mice lacking hypocretin, in which the hypocretin gene has been knocked down, are much less induced in their prey.
sleep fraction
What happens to the sleep of the elderly? Lee et al. show that with age, changes occur in these hypocretin-producing neurons. They become over-stimulated at the slightest provocation, conducting signals at very low thresholds and releasing neuropeptides. Unwanted activation of dormant hypocretin neurons leads to the splitting of sleep. Changes in aged neurons thus make it more difficult to inhibit their activity.
Hcrt/OX is a rare disorder of the nervous system triggered by the loss of neurons. There are peculiar features of narcolepsy – an excessive desire to sleep during the day, even if the total number of hours of sleep remains unchanged; Tendency to hallucinate due to blurred sleep-wake phases; Repeated loss of muscle tone – cataplexy – during which the muscles loosen. Only a few cases have been documented in India, mostly men in their thirties (Re, Indian Journal of Medical Research, 148, 748 (2018)). Patients with this condition have missing amounts of hypocretin in their cerebrospinal fluid.
Finally, can sufferers of fragmented sleep dream of ways to bring better stability to their sleep? In aged rats, the analgesic flupirtine, although beset with toxicity issues, raises back the threshold at which hypocretin neurons are stimulated, thus restoring the structure of sleep.
(The article was written in collaboration with Sushil Chandani who works in Molecular Modelling. sushilchandani@gmail.com)
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