Sleep physiology and stages of sleep cycle

Physiology of sleep and stages of sleep

1. SLEEP

2. Sleep  Sleep is a rapidly reversible state of reduced responsiveness, motor activity, and metabolism

3. Wake Some of the neuronal clusters that significantly contribute to the brain activation of wakefulness include dorsal and caudal raphe neurons located in the pons and medulla, respectively (serotonin-containing);

4. Wake Noradrenaline Histamine Dopamine Orexin / hypocretin -containing ; acetylcholine-containing the reticular formation (glutamate-containing)

5. Non-REM Sleep The chief cell groups that comprise this non-REM sleep-active inhibitory system include neurons in The non-REM sleep-active GABA neuronal groups include those in the ventrolateral preoptic region of the thalamus, ventrolateral preoptic area of thalamus and anterior region of the hypothalamus, and regions of the basal forebrain. The cell groups that comprise this non-REM sleep-active inhibitory system synthesize and secrete the inhibitory amino acid gamma- aminobutyric acid (GABA) and the neuropeptide galanin

6. GABA 1)ascending cortical activation activation of cortically projecting inhibitory GABA neurons is responsible for the relatively higher-voltage and slower-wave EEG activity that typifies non-REM sleep

7. REM REM sleep, on the other hand, is associated with the dreaming phase of sleep and is accompanied by paralysis ( atonia ) of the skeletal musculature, effects that can also impact breathing.

8. REM There are two major circuits involved in REM sleep generation . 1)ascending cortical activation and 2) descending spinal motor inhibition The activation of these circuits produces the defining signs of REM sleep: (1) low-voltage

9. REM and fast-wave EEG activity and suppression of postural motor tone. Important for the changes in EEG activity is reactivation of the cholinergic cell groups in the pons and basal forebrain that were relatively inactivated during non-REM sleep .

10. REM The spinal motor activity in REM sleep is suppressed through recruitment of descending neural circuits that involve glycine (principally) and GABA

11. REM However, the periods of major suppression of upper airway muscle activity that are also seen in REM sleep do not seem to involve the same mechanism. The genioglossus muscle activity in REM sleep is suppressed through two additional processes: (1) disfacilitation (i.e., withdrawal of excitatory inputs), mediated principally by reduced noradrenaline and serotonin excitation at the hypoglossal motor pool, and (2) inhibition mediated by a newly identified muscarinic receptor mechanism linked to G protein–coupled potassium channels

12. THE “SLEEP SWITCH”

13. TONGUE

14. PHYSIOLOGY The neural respiratory cycle comprises three phases Inspiration (TI) involves ramplike increases in inspiratory motor neuron firing, which drive phrenic nerve activity throughout this phase . The first phase of expiration (TE1) is often called post-inspiration, because inspiratory motor neurons are still active. Persistent inspiratory motor activity during TE1, which declines throughout this phase, acts to slow the exit of air from the lungs . The second phase of expiration(TE2 ), expiratory muscles are typically electrically silent. During this phase of passive relaxation, gas is expelled as the lungs and chest wall return to their equilibrium state (i.e., functional residual capacity).

15. Physiology However, under conditions where respiratory drive is increased, expiratory muscles including the internal intercostal and abdominal muscles become active during TE2. This notion is an example of how the central controller, influenced by sensory feedback, modulates and alters the integrated motor response of the system.

16. Centre

17. RESPIRATORY CENTRAL PATTERN GENERATOR (RCPG) ventral respiratory column (VRC) is orientated in the rostral -to-caudal direction. The VRC extends from the retrotrapezoid nucleus (RTN) adjacent to the rostral facial nucleus (VII) superiorly, to the caudal ventral respiratory group ( cVRG ) near the spinomedullary junction inferiorly.

18. The main areas of rhythmically active VRC respiratory neurons are in the Bötzinger complex ( BötC ) pre- Bötzinger complex (pre- BötC ), rostral ventral respiratory group ( rVRG ), and cVRG . The parafacial respiratory group ( pFRG ) overlaps anatomically with the RTN,

19. these regions include intrinsically bursting neurons which may contribute to rhythm generation. Peripheral chemo- and mechanosensory inputs are transmitted to the nucleus of the solitary tract ( nTS ) in the dorsal respiratory group (DRG).

20. The pontine respiratory group (PRG) includes the Kölliker –Fuse (K–F) and the parabrachial (PB) nuclei which contain respiratory-modulated neurons

21. The ventral respiratory group (VRG) contains Bötzinger complex (expiratory) neurons , pre- Bötzinger complex ( inspiratory ) neurons, rostral ventral respiratory group (predominantly inspiratory ) neurons, and caudal ventral respiratory group (predominantly expiratory) neurons.

22. The dorsal respiratory group (DRG) contains mainly inspiratory neurons. The DRG and its associated regions of the nucleus of the solitary tract are also the projection sites for afferents important to the reflex control of breathing: the carotid and aortic chemoreceptors and baroreceptors , and lung vagal afferents.

23. Neuronal populations in the Bötzinger complex ( BötC ) are the major source of expiratory network activity during normal breathing. Thus , BötC neurons are important for control of the transition between inspiratory and expiratory activities in the rCPG and maintenance of the rhythmicity of normal breathing

24. Neurons within the PRG are critical for formation of normal resting breathing patterns . Functional connections between the pons and the rest of the rCPG modulate phase switching (onset and termination of inspiration).

25. For example, the dorsolateral pons ( dlPons ) is a region within the PRG with respiratory-modulated neurons whose activity varies depending on the presence of vagal afferent feedback.

26. eupneic breathing patterns are dependent on excitatory drive from pontine neurons to the VRC

27. Medullary raphé nuclei likely represent a system of intermediate relays for signaling between the PRG and the VRC. The medullary raphé are chemosensitive , responding to local changes in carbon dioxide or pH, as well as exhibiting altered activity with stimulation of peripheral chemoreceptors .

28. The rostral ventral respiratory group ( rVRG ) region within the VRC comprises excitatory neurons that drive spinal phrenic and intercostal inspiratory motor neurons . This group of neurons is inhibited by the BötC during expiration and excited by the pre- BötC during inspiration.

29. These rhythmically alternating influences, along with modulatory inputs from other areas of the pontomedullary network, are responsible for shaping and controlling the pattern of inspiratory rVRG activity. In contrast, the cVRG is thought to be the expiratory counterpart to rVRG activity.

30. Peripheral chemo- and mechanosensory inputs are transmitted to the nTS , which contains secondorder neurons critical for reflex respiratory responses. For example, carotid body chemoreceptorand baroreceptor afferents terminate in the medial and lateral subnuclei of the nTS

31. mechanoreceptors have projections to “pump cells” in the nTS , resulting in rhythmic activity of these cells which is modulated by lung inflation. The retrotrapezoid nucleus (RTN) is a site of centralchemoreception . Chemoresponsive neurons within this region project to other areas of the rCPG and provide excitatory drive to the VRC and PRG.

32. As part of the respiratory neural network, the nTS modulates breathing via projections to both pontine and ventral medullary components of the central respiratory network. In addition, neurons within the nTS receive inspiratory drive from the VRC and reciprocal pontine projections gate neuronal activity in the nTS .