Brain Mechanisms of Sleep: Arousal Systems

• Serotonin system originates in raphe nuclei, with widespread projections to various brain regions including thalamus, hypothalamus, basal ganglia, hippocampus, and cortex. Stimulation of this system causes cortical arousal and may facilitate continuous movements such as pacing, chewing, and grooming. Serotonin levels decrease during deep sleep.
• Histamine system originates in the tuberomammillary nucleus in the hypothalamus, with projections to cortex, thalamus, basal ganglia, and hypothalamus. Activity is high during waking and low during sleep. Histamine antagonists increase sleep, and histamine mutants show normal spontaneous wakefulness but less arousal in response to environmental stimuli.
• The lateral hypothalamus is the origin of another arousal system, with widespread projections to the cortex and modulatory systems. This system has an excitatory effect on these modulatory systems and is active during exploration, with low activity during sleep.
• Lesions of the lateral preoptic area result in total insomnia and eventually death. Electrical stimulation of this area produces signs of drowsiness, and there is a "flip-flop" mechanism where the sleep-promoting region in the lateral preoptic area is inhibited, and brain system and forebrain arousal systems are activated, while the flip-flop is off when these systems are inhibited, and the sleep-promoting lateral preoptic area is activated.
• Orexins, a neuropeptide system, cause motivation to stay awake and help counteract sleep pressure, keeping the flip-flop interaction stable. Orexin's role may be crucial in the circadian rhythm, hunger, and satiety signals. Orexin mutant mice exhibit more frequent shifts between sleep and waking states but normal amounts of sleep and waking.
• Sleep stages are studied using EEG, with distinct patterns of awake, deep sleep (stage 3 and 4), and REM sleep. During wakefulness, there is low amplitude, high frequency desynchronized activity due to a large proportion of neurons firing out of sync. During deep sleep, there is low frequency, high amplitude synchronous activity. During REM sleep, there is desynchronized rapid, irregular EEG activity with rapid eye movements, muscle paralysis, and deep relaxation, along with the potential for vivid dreaming.
• REM sleep is controlled by a REM flip-flop mechanism, and it is essential for development, with approximately 70% of sleep in a newborn being REM. REM sleep may also be important for motor learning and improvement of learned behaviors, as motor components of dreams may be crucial.
• The suprachiasmatic nucleus (SCN), located above the optic chiasm, controls the internal circadian clock by responding to light cues and maintaining a circadian rhythm. SCN lesions disrupt both the entrainment to light cues and the internal (free-running) clock, indicating that the SCN is responsible for the intracellular ticking that maintains the circadian rhythm. The SCN shows increased metabolic activity during the day and has a circadian cycle of its own, evident in both nocturnal and diurnal animals.
• The molecular control of SCN intracellular ticking involves negative feedback, where a protein inhibits its own production when it reaches a certain level.

Explore the role of acetylcholine, norepinephrine, serotonin, histamine, and orexin in controlling an animal's level of alertness and wakefulness. Understand their impact on cortical arousal, alertness, memory, and attention during various sleep stages.