1. RETICULAR FORMATION, SLEEP AND WAKEFULNESS
PHYSIOLOGY
Raquel Duarte

2. RETICULAR FORMATION
Diffuse mass of neurons & nerve fibers that make the core of the brain stem;
They run through the medulla oblongata, pons & midbrain;
Nc. of medullary reticular formation;
Nc. of pontine reticular formation;
Nc. of midbrain reticular formation;

3. RETICULAR FORMATION –AFFERENT & EFFERENT CONNECTIONS OF RETICULAR FORMATION
Optic, auditory olfactory and taste pathways
Sensory Pathways
Cerebellum
Substancia Nigra
Thalamus
Cortex
Reticular Formation
Red Nucleus
Reticular Formation
Cerebellum
Cortex SC SC
Tectum
(Touch, pain, temperature, kinesthestic sensation)
Thalamus, Hypothalamus
Corpus Striatum
EFFERENT CONNECTION TO THE RETICULAR FORMATION
AFFERENT CONNECTION TO THE RETICULAR FORMATION

4. FUNCTIONAL DIVISIONS OF RETICULAR FORMATION
RETICULAR ACTIVATION SYSTEM (RAS)
Name given to
RETICULAR FORMATION & ITS CONNECTIONS
It’s believed to be the center of arousal and motivation in mammals (including humans).
ASCENDING RETICULAR ACTIVATION SYSTEM
DESCENDING RETICULAR ACTIVATION SYSTEM

5. ASCENDING RETICULAR ACTIVATION SYSTEM - ARAS
Receives fibers from the sensory pathways via long ascending spinal tracts.
Alertness, maintenance of attention and wakefulness.
Emotional reactions, important in learning processes.
Tumor or lession – sleeping sickness or coma.

6. DESCENDING RETICULAR ACTIVATION SYSTEM - DRAS
INHIBITORY
Smoothness and accuracy of voluntary movements;
Reflex movements;
Regulates muscle tone;
Maintenance of posture;
Control of vegetative functions.
FACILITATORY
Maintains the muscle tone;
Facilitates autonomic functions;
Activates ARAS.

7. RETICULAR FORMATION: FUNCTIONS
REGULATION OF SLEEP, thus, the maintenance of the SLEEPING cycle or CIRCADIAN rhythm;
Filtering of incoming stimuli to discriminate irrelevant background stimuli;
It’s crucial to maintain the state of CONSCIOUSNESS related to the circadian rhythm – MELATONIN effects on RAS;
ANS control – respiratory rate, heart rate, GIT activity.

8. SLEEP
Unconciousness state from which a person can be aroused by sensory or other stimuli;
Has multiple stages: from very deep to very light sleep;
It’s divided into two entirely different types of sleep that have different quantities & alternate: slow- wave sleep (NREM) & rapid eye movement sleep ( REM).

9. SLEEP & BRAIN WAVES
Determined by the level of excitation of different parts of the brain resulting from sleep, wakefulness or brain diseases (epilepsy and psychosis).
Measured by
“Electroencephalography (EEG) is the measurement of electrical activity produced by the brain (cortex) as recorded from electrodes placed on the scalp.“

10. SLEEP : SLOW- WAVE SLEEP
In this type of sleep the brain waves are very strong & show a low frequency;
Occurs during the first hour after going to sleep & it’s exceedingly restful;
↓ of peripheral vascular tone & other vegetative functions of the body, such as: a 10 to 30 % ↓ in BP, in respiratory rate & in basal metabolic rate;
Called “dreamless sleep”, although dreams do occur during this phase.
The difference between this and REM sleep is that they’re associated with less bodily muscle activity & also that during this phase the consolidation of dreams in memory doesn’t occur.

11. SLEEP : SLOW- WAVE SLEEP
More restful type of sleep;
Associated with (viscero-)motor activities;
4 Phases:
- I (Drowsiness): low voltage fluctuations, alpha waves reduced;
II (Light sleep): low voltage of delta waves;
III (Medium sleep): frequency of delta waves reduced, amplitude increases;
IV (Deep sleep): delta waves more prominent, low frequency and high altitude.

12. SLEEP : REM ( RAPID EYE MOVEMENT) SLEEP, PARADOXICAL SLEEP, DESYNCHRONIZED SLEEP
Bouts of REM sleep last for 5 to 30 min & usually appear on average every 90 minutes;
As the person becomes more rested during the night, the durations of the REM bouts ↑;
REM characteristics:
Active dreaming & active bodily muscle movements;
The person is more difficult to arouse by sensory stimuli than during the deep slow- wave sleep & people usually awaken spontaneously during a REM episode;
Muscle tone is exceedingly depressed – strong inhibition of the spinal muscle control areas;
Heart rate & respiratory rate become irregular;
Irregular muscle movements occur;
Brain is ↑ active & brain waves are similar to those of wakefulness.

13. SLEEP : REM ( RAPID EYE MOVEMENT) SLEEP, PARADOXICAL SLEEP, DESYNCHRONIZED SLEEP
5-30 minutes long, every 90 minutes;
↓ muscle tone;
↑ brain metabolism ( as much as 20 % );
Irregular heart and respiratory rate;
Rapid eye movements;
Less restful, desynchronised;
Associated with psychical activities, such as dreaming.

14. Also called the SLEEPING CYCLE
REGULATION OF SLEEP
CIRCADIAN RHYTHM
24 hours cycle in BIOCHEMICAL, PHYSIOLOGICAL & BEHAVIOURAL processes of living organisms
Also called the SLEEPING CYCLE
The CIRCADIAN RHYTHM is differentiated from other coincidental or apparent cycles according to three general criteria:
Rhythm persists in constant conditions within a period of 24h (absence of external stimuli);
Rhythm is temperature-compensated;
Rhythm can be reset by exposure to external stimuli.

15. CIRCADEAN RHYTHM SAD ( Seasonal Affective Disorder)
Disturbances to the rhythm
SAD ( Seasonal Affective Disorder)
DSPS ( Delayed Sleep Phase Syndrome)
Among others ( fatigue, insomnia, bipolar disorders, sleep disorders, …).
The classic phase markers for the measuring of the circadian rhythm are
MELATONIN secretion by the pineal body
BODY TEMPERATURE
Melatonin is absent or undetectibly low during the day;
Dim- Light Melatonin Onset ( DLMO) is at +- 9 p.m.;
Melatonin offset & sleep offset were found to be related recentently.

16. SLEEP DISORDERS Insomnia; Hypersomnia; Narcolepsy and Cataplexy;
Sleep Apnea Disorder;
Nightmare & Night Terror;
Somnambulism;
Nocturnal Enuresis;
Movement Disorders during sleep.

17. REGULATION OF SLEEP
Stimulation of certain specific areas of the brain can produce sleep with characteristics near those of natural sleep, such as:
The raphe nuclei in the lower half of the pons & in the medulla;
The nucleus of the tractus solitarius;
Several regions of the diencephalon, such as rostral portion of the hypothalamus ( mainly in the suprachiasmal area) & an occasial area in the diffuse nuclei of the thalamus.
Which send fibers to the brain stem reticular formation & also to the hypothalamus, thalamus, most of the areas of the limbic system, to the neocortex & also to the SC;
Many nerve endings from these fibers produce SEROTONIN, that if blocked doesn’t allow the production of sleep for several days.

18. Lesions in the raphe nuclei lead to high state of wakefulness;
REGULATION OF SLEEP
Lesions in the raphe nuclei lead to high state of wakefulness;
Bilateral lesions in the medial rostral suprachiasmal area in the anterior hypothalamus also cause wakefulness;
In both cases, the excitatory reticular nuclei of the mesencephalon and upper pons become released from inhibition, thus causing INTENSE WAKEFULNESS
These type of lesions can lead to death of the animal due to exhaustion.

19. There are also other possible transmitter substances related to sleep
REGULATION OF SLEEP
There are also other possible transmitter substances related to sleep
It has been shown that in the CSF, in blood or urine of animals kept awake over a long period, there are substances that cause sleep when injected into the brain ventricular system of another animal.
MURAMYL PEPTIDE in CSF;
Another nonpeptide isolated from blood of sleeping animals;
Another unidentified substance found in the neuronal brain stem of animals, causes the accumulation of sleep factors ( in CSF or in the brain stem) leading to sleep.

20. BASIC THEORIES OF SLEEP
PASSIVE THEORY OF SLEEP: this earlier theory of sleep said that the RAS became simply fatigued during the day & as a result inactivated during the night;
It was later proved that sleep is caused by an active inhibitory process, once that there seems to be a center located below the midpontile level of the brain stem that is required to cause sleep by inhibiting other parts of the brain;
ONTOGENIC HYPOTHESIS OF REM SLEEP says that the activity occurring during neonatal REM sleep (or active sleep) seems to be particularly important to the developing organism. Deprivation of active sleep early in life was shown to result in behavioral problems, permanent sleep disruption, decreased brain mass.

21. PHYSIOLOGICAL CHANGES DURING SLEEP
Plasma volume decreases;
Heart rate decreases;
Blood pressure decreases;
Rate and force of respiration decreases;
Salivary secretion decreases;
Secretion of gastric juice does not alter or slightly increases;
Formation of urine decreases;
Sweat secretion increases;
Lacrimal secretion decreases;
Muscle tone and reflexes decrease except ocular muscles;

22. PHYSIOLOGICAL EFFECTS OF SLEEP
Sleep has two major effects: at the level of the nervous system & at the level of other functional systems of the body;
The effects on the CNS are far more important; prolonged wakefulness is associated with progressive malfunction of the thought processes & can cause abnormal behavioural activities;
Sleep, in multiple ways, restores both NORMAL LEVELS OF BRAIN ACTIVITY & NORMAL BALANCE AMONG THE DIFFERENT FUNCTIONS OF THE CNS;
“ The principal value of sleep is to restore the natural balances among the neuronal centers.”

23. CYCLE BETWEEN SLEEP & WAKEFULNESS
There’s yet no explanation for the reciprocal operation of the sleep-wakefulness cycle;
But some suggest that when the sleep centers are NOT activated, the mesencephalic & upper pontile RAS are released from inhibition, which allows the RAS to become spontaneously active;
This will excite PNS & Cerebral Cortex, both of which send POSITIVE FEEDBACK to the same reticular activating nuclei to activate them still further;
So, once wakefulness starts it has a natural tendency to sustain itself;
After a few hours, the brain & even neurons themselves become fatigued & the positive feedback fades & sleep- promoting centers take over.

24. BIBLIOGRAPHY Medical Physiology, 11th Edition, Guyton & Hall
Physiology at a Glance, Ward, Clarke & Linden

25. Thank you for your attention!