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5HT and Sleep

SINCE ANTIQUITY, dreams have evoked curiosity and wonder. Biblical characters found prophecies in them. Freud, in "The Interpretation of Dreams," published more than 100 years ago, called them "the royal road to a knowledge of the unconscious activities of the mind."

Modern neuroscientists see the function of sleep and dreaming as slightly more mundane-but nonetheless critical to health. Without sleep, our moods and our memories-even our immune systems-would be profoundly compromised.

Dr. J. Allan Hobson, professor of psychiatry at Harvard Medical School and director of the Laboratory of Neurophysiology at the Massachusetts Mental Health Center, has spent more than 40 years studying sleep and dreaming. He is author of "The Chemistry of Conscious States" (Little, Brown, 1994).

He describes how our brain chemistry cycles from the dominance of one chemical system to another during wakefulness, slow wave sleep and REM sleep (rapid eye movement sleep, during which most, but not all, dreams occur).

"In order to be awake and aware," he said, "the brain needs two chemicals: noradrenaline and serotonin."

During slow wave sleep (most of the sleep during the night), the levels of these chemicals fall by half. During REM sleep, the levels drop to nearly zero, and brain activity is dominated by neurons using another chemical: acetylcholine.

According to Hobson, during sleep when acetylcholine systems dominate, the noradrenaline and serotonin neurons use this "downtime" to regenerate their transmitters. Acetylcholine systems remain active in both sleep and wakefulness, however.

The two systems work in contrast with each other, so if there is too much activity in one, the other will attempt to slow it down and vice versa with too little activity.

The balance between these systems is lost during depression and other mood disorders, however-which is why sleep disturbances (either too much or too little) almost always accompany depression. Drugs used to treat depression-like Prozac-tend to increase the activity of the serotonin system.

"The serotonin system is like the heart of the brain," said Hobson. "Its cells are like the pacemaker cells of the heart. They fire automatically and rhythmically and send axons all over the brain."

In fact, the heart itself actually includes serotonin receptors, and some researchers believe this may account for the link seen between cardiac problems and depression.

Hobson says that sometimes the serotonin antidepressants (SSRIs) like Prozac end up causing disruptions of their own. REM sleep disorder, in which people physically act out their dreams, has occurred in some patients taking these drugs. "SSRIs can raise hell with motor systems in sleep," said Hobson. "It's appropriate to warn people at this point, but not to panic. There is just no free lunch if you play with sleep control systems."

Serotonin and noradrenaline are also necessary for attention and memory.

"In order to have this conversation, there are cells firing all the time," Hobson said. "The minute you start to lose attention, the levels of serotonin and noradrenaline start to fall." The disturbances of concentration and memory seen in depression are probably accounted for by this connection.

Most dreams aren't pleasant-raising another possible connection between sleep and mood problems. Hobson's group has found that during dreams, three emotions dominate: anxiety, anger and elation, meaning your odds are two in three of feeling bad in a dream.

"These emotions could fit into the depressive spectrum , but in dreams, the aminergic [dopamine and noradrenaline] deficit is acute and restored immediately upon waking. Depression takes days or weeks to develop."

Dreams are hard to remember because noradrenaline and serotonin are virtually unavailable during REM sleep. These substances are needed to record memories. You can recall a dream that immediately preceded awakening, because the noradrenaline and serotonin systems come back online as you wake up. But if you shift your attention at all while you wake, you will often find that the memory of the dream vanishes.

Recent research shows that during dreaming, the rational, decision-making part of the brain is quiet while emotional areas take over.

"In dreams, you don't know where you are, you can't remember things, there is no analytic capability, but perception and emotions are very strong," said Hobson, explaining that this is linked to the lack of activity in the prefrontal cortex and increased activity in central brain areas.

He also pointed out that dreams are "hyper-associative," with scenarios shifting from one to another via connections and associations probably known only to the dreamer. A body of evidence now shows that one function of dreaming and sleep is memory consolidation and processing, which might explain these weird associations. Sleep-deprived people remember less well, and skills learned before sleep actually improve (with no additional practice) upon awakening.

"Memory is probably organized in several ways in the brain," Hobson said. "There is meta-knowledge [knowledge about how you know things and deal with them], orientation knowledge-which is probably emotionally guided so that when you walk out the door, you know whether a place is dangerous or not, and also procedural knowledge. Walking and other banal things we take for granted-these systems are not trivial to maintain. Try walking without a mechanism [for doing it without conscious thought]."

Sleep and dreaming help maintain your brain's information systems.

"You run the system offline and tie in new information according to some rules," said Hobson.

Though many say lack of sleep can't kill you, in fact, if you went without for long enough, it could. Sleep is crucial to immune function, and animals deprived of it often die of infections.

Evolutionarily, sleep has several purposes, though it might appear to make an animal more vulnerable to predators.

"It makes sense to get animals off the street at night," Hobson said. "It is thermally efficient and it reinforces biologically significant connections between couples and families."

Hobson's next book will deal with psychedelic drugs. Interestingly, LSD acts on the serotonin system, though in a quite different way than antidepressants do. The book will examine how LSD trips are virtually "dreaming while awake" and what psychedelics can help scientists learn about the brain.