Non-REM & REM Sleep Physiology


  • The anatomic location of the sleep center
  • The physiology of the thalamocortical circuits
  • The pathway for the generation of REM sleep.

Historical Background

  • Baron Constantin von Economo first hypothesized about the anatomy of the sleep induction center when in 1916–17 he studied the clinical–pathologic correlations of patients who had died from encephalitis lethargica (aka von Economo’s encephalitis).
  • The parkinsonian and oculomotor manifestations found in patients with that disorder led him to postulate that:
    • The sleep induction center lies within the anterior hypothalamus
    • The area for wakefulness lies, roughly, within the posterior hypothalamus/upper brainstem

Over the next several decades, he was proven, to a large extent, correct.


  • The area for non-REM sleep induction lies within the anterior hypothalamus, specifically in the ventrolateral preoptic area and the median preoptic nucleus.


Thalamocortical network

  • Thalamocortical network generation of sleep electroencephalographic (EEG) patterns — sleep spindles and slow-wave sleep.

Major cell populations

  • GABAergic reticular thalamic neurons (thalamus)
  • T-type calcium channel thalamocortical neurons (thalamus)
  • Cortical pyramidal cells (cerebral cortex)


  • The reticular thalamic nuclei gate the flow of information between the thalamus and cerebral cortex, and the thalamocortical neurons drive cortical EEG patterns through, at least in part, the low-threshold spike.
  • The reticular thalamic nuclei causes GABAergic inhibition of thalamocortical cells.
  • Eventually the thalamocortical membrane hyperpolarizes more negatively than –65 mV, which causes the T-type calcium channels to open, which generates a low-threshold spike: a burst of action potentials.
  • The thalamocortical burst acts both on the reticular thalamic cells to facilitate their rhythmic oscillation and also on the cortical pyramidal neurons, which generate the EEG patterns observed during sleep.
  • After the low-threshold spike, there is a refractory period for the thalamocortical neurons.
  • As a byproduct of the refractory period, there is cessation of the excitatory thalamocortical inputs to such relay neurons as the lateral geniculate nucleus, which results in the phenomenon of sensory gating: the process wherein sensory stimuli that might otherwise wake us from sleep fail to reach our cerebral cortex.


  • The putative primary REM-promoting region lies within the pons, in what is called the sublaterodorsal nucleus in the rat and the perilocus coeruleus in the cat.
    • This region excites the cortex to produce the characteristic EEG pattern of REM sleep.
    • And also excites a constellation of nuclei called the supra-olivary medulla to produce muscle atonia during REM sleep.
  • REM inhibition comes from the midbrain (during wakefulness and non-REM sleep) from the ventrolateral periaqueductal gray area and the dorsal deep mesencephalic reticular nucleus, which tonically inhibit the sublaterodorsal nucleus/peri-locus coeruleus.
  • REM disinhibition comes from the hypothalamus, from lateral hypothalamic melanin concentrating hormone nuclei, and from the medulla, from the dorsal paragigantocellular nucleus, which suppress the REM inhibition subnuclei and frees the REM promoting region to act on the supra-olivary medulla and cerebral cortex to produce REM sleep as previously described.

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