How Is Sleep Regulated?

What is the difference between sleep and wakefulness? Much of it depends on which brain systems are activated.

Wakefulness is maintained by several brain systems, each regulating different aspects of this state. Many of the systems are located in the upper brainstem, where nerve cells using the neurotransmitters acetylcholine, norepinephrine, serotonin, and glutamate connect with the forebrain. Nerve cells containing orexin, in the hypothalamus, are also important in wakefulness — and, as mentioned above, their loss causes narcolepsy. Hypothalamic nerve cells containing the neurotransmitter histamine play a key role as well. Activation of the thalamus and the basal forebrain by acetylcholine is particularly important in maintaining activity in the cerebral cortex and consciousness. This level of alertness is reflected in an activated, low-voltage EEG.

During non-REM sleep, these arousing systems become much less active, and the transmission of information from the senses through the thalamus is curtailed. Consciousness lessens, and wakefulness gives way to the slow wave pattern typical of the first stage of sleep. During this state, there is active suppression of arousal systems by a group of nerve cells in the hypothalamus, called the ventrolateral preoptic (VLPO) nucleus. The cells in the VLPO contain the inhibitory neurotransmitters galanin and GABA. Damage to the VLPO nucleus produces irreversible insomnia.

The state of REM sleep is characterized by an internally activated brain and an activated EEG — but with external input suppressed. Internal activation during REM comes from a cyclically active REM sleep generator made up of neurons in the brainstem. Signals from these neurons cause the forebrain to become excited and lead to the rapid eye movements and muscle suppression — hallmark signs of this state. In the absence of external input, forebrain excitation from internal sources is the driving force behind the vivid dreams experienced during REM sleep. Interestingly, our motor cortex nerve cells fire as rapidly during REM sleep as they do during waking movement, a fact that explains why movement can coincide with dreams. The periodic recurrence of REM sleep about every 90 minutes during sleep is thought to be caused by the on-off switching of REM-generating neurons, which produce acetylcholine and glutamate, and REM-suppressive neurons, which produce norepinephrine, serotonin, and GABA.