Neurophysiology of Wakefulness and NREM Sleep
Maintenance of wakefulness is driven by the ascending reticular activating system (ARAS). A tonic stream of excitatory impulses from the brainstem reticular formation and thalamus maintains the cortex in an alert state. The EEG shows desynchronization—low-amplitude, high-frequency activity (beta rhythm). Meanwhile, excited neurons in the frontal cortical regions exert an inhibitory influence on hypothalamic sleep centers, maintaining the status quo.
Transition into non-rapid eye movement (NREM) sleep is associated with decreased activity of activating structures (posterior hypothalamus, locus coeruleus, raphe nuclei).
- Cortical inhibition on the hypothalamus is lifted, and hypothalamic sleep centers become excited, actively inhibiting the reticular formation.
- GABAergic neurons of the thalamus and basal forebrain suppress the activating systems.
- A functional blockade of sensory inputs occurs.
The EEG exhibits synchronization: sleep spindles, K-complexes, and delta waves appear. The duration of this phase is mediated by the delta-sleep-inducing peptide and the accumulation of uridine.
Mechanisms of Paradoxical (REM) Sleep
The genesis of rapid eye movement (REM) sleep is closely linked to the activity of the dorsal pontine tegmentum. Although the EEG demonstrates secondary desynchronization (the "awake brain"), afferent sensory input is restricted, and efferent motor output is completely shut down, resulting in muscle atonia.
According to the Hobson-McCarley reciprocal interaction theory, brainstem structures play a key role in phase transitions:
- During wakefulness, the locus coeruleus is active, inhibiting giant neurons of the reticular formation.
- During the transition to sleep, this inhibitory influence weakens.
- In the REM phase, a sharp activation of giant reticular formation neurons occurs due to the release of acetylcholine.
The central region of the reticular formation triggers rapid eye movements (REMs), while its posterior portion blocks muscle tone via projections to the spinal cord. Dreams occur because the excitation of ganglionic neurons activates the cortex and memory processes, generating visual imagery. The duration of the paradoxical phase is regulated by glutathione.
Molecular Mechanisms of the Biological Clock
The sleep-wake cycle is governed by the master circadian pacemaker—the suprachiasmatic nuclei of the hypothalamus (SCN). Its function is based on a negative feedback loop at the genome level:
- Activation: Specific intracellular proteins BMAL1 and CLOCK assemble into an active dimer. This complex enters the cell nucleus, binds to the E-box promoter on DNA, and initiates transcription of clock genes (PER-1, PER-2, PER-3).
- Synthesis: The resulting mRNA enters the cytoplasm, where PER proteins are translated on ribosomes.
- Inhibition: Accumulated PER proteins form a repressor complex that binds to BMAL1/CLOCK and blocks their activity.
As a result, transcription and translation halt. When the concentration of inhibitory proteins drops due to their degradation, the cycle restarts. An external humoral modulator of these rhythms is melatonin, secreted by the pineal gland—rising levels initiate the transition to sleep.