Funkcionális neuroanatómia 12.

1. Funkcionális neuroanatómia 12. Az alvás és ébrenlét, aktiválódás, figyelem és az elhatározás neuroanatómiája 2012 - Neuromorfológia PhD program

2. William Howell (1860-1945). Late in the nineteenth century, Howell proposed that sleep could have multiple interacting causes. He looked upon cerebral anemia and blood flow as being especially important factors. Constantin von Economo (1876-1931), who studied patients with viral encephalitis and concluded sleep might be caused by damage to the periventricular gray matter of the brainstem. Johann Friedrich Blumenbach (1752-1840). Blumenbach examined a young man with an opening in his skull. He observed that his brain seemed to press upon his skull when he was awake and seemed to shrink when he was asleep. Blumenbach concluded that sleep was caused by a diminished flow of blood to the brain.

3. Reticular formation

4. mesencephalic reticular formation promotes the walking state medullary reticular formation inhibits the walking state(sleep induction)

7. The major regions of the brain stem and forebrain involved in sleep control. Stimulation of neurons in the nucleus reticularis pontis oralis/caudalis (RPO/RPC) region produces various characteristics of sleep. Depending on their exact size and location, bilateral lesions within this region completely block REM sleep or block components of REM sleep. CG – central gray; LC – locus ceruleus; LDT – lateral-dorsal tegmental nucleus; PPN – pedunculopontine nucleus.

8. ébrenlét wakefulness

10. Spinoreticulothalamic tract „ascending reticular activating system” A thalamus intralaminaris magjaiból eredő thalamo-corticalis rostok számos kérgi területen végződnek: a prefrontalis kéregben, az elülsőcinguláris kéregben, a premotoros areában, az insularis kéregben és a parietális asszociációs area neuronjain.

11. The ascending arousal system sends projections from the brainstem and posterior hypothalamus throughout the forebrain.Aminergic nuclei (green circles) diffusely project throughout much of the forebrain, regulating the activity of cortical and hypothalamic targets directly. Neurons of the tuberomammillary nucleus (TMN) contain histamine (HIST), neurons of the raphé nuclei contain 5-HT and neurons of the locus coeruleus (LC) contain noradrenaline (NA).

12. Phd 050519 Neurotranszmitterek 25. dia Cholinerg sejtcsoportok medial septal Ch1 nucleus of the diagonal band Ch2-Ch3 nucleus basalis (Meynert) Ch4 laterodorsal tegmental nucleus Ch5 pedunculopontine nucleus Ch6 Ch5 and Ch6 cholinerg neurons - coexpress substance P, ANF and CRF, - fibers ascend in the dorsal tegmental bundle, - innervate intralaminar, anterolateral and mediodorsal thalamic nuclei. In wakefulness and REM sleep: cholinerg neurons fire rapidly.

14. sleep

15. Kétféle alvás és szinonímái slow-wave sleep NREM sleep non-REM sleep synchronized sleep S sleep rapid eye movement sleep REM sleep paradoxical sleep desynchronized sleep D sleep

16. brain areas involved in sleep ascending reticulothalamic system (NREM)

17. slow-wave sleep NREM sleep

18. Neurons of the laterodorsal tegmental nuclei and pedunculopontine tegmental nuclei (LDT and PPT) (blue circles) send cholinergic fibers (ACh) to many forebrain targets, including the thalamus (LG+VLP), which then regulate cortical activity. Aminergic nuclei (green circles) diffusely project throughout much of the forebrain, regulating the activity of cortical and hypothalamic targets directly. Neurons of the tuberomammillary nucleus (TMN) contain histamine (HIST), neurons of the raphé nuclei contain 5-HT and neurons of the locus coeruleus (LC) contain noradrenaline (NA).

19. Non-REM sleep • Midbrain reticular formation neurons inhibited. • The generated rhythmic firing of thalamic relay neurons is depleted(a result of GABAergic inhibitory neurons in the nucleus reticularis) = hyperpolarization of thalamo-cortical neurons. • EEG spindles, low waves produced by synchronized synaptic potentials in cortical neurons = NREM sleep.

20. NREM sleep jellemzői neuronal activity is low, parasympathetic activity predominates, slightly reduced pulmonary (alveolar) ventillation, declined heart rate and blood pressure, increased gastrointestinal motility, deminished kidney filtration, declined basal metabolic rate, falled body temperature, decreased sympathetic outflow, intact muscle tone and reflexes

21. Non-REM sleep stages stage 1) Transition from wakefulness to sleep mixed frequencies – low voltage no rapid eye movements some skeletal muscle activities stage 2) Sleep spindles (sinusoidal waves) high amplitude low voltage stage 3) High amplitude – (reflects activity in the prefrontal cortex) slow delta waves stage 4) Increased slow-wave activities loss of muscle tone

22. NREM sleep EEG hullámai

23. REM sleep

24. brain areas involved in sleep ascending reticulothalamic system (NREM) pontine-geniculo-occipital (PGO) axis (REM)

25. REM sleep jellemzői • neuronal activity is high in the pontine reticular formation, lateral geniculate body, occipital cortex neurons (PGO spikes), • overall increase in neuronal activity during REM sleep, • muscle tone is generally reduced, except eye movements, breathing, • dreaming, • changes of heart rate and blood pressure, • EEG enters a desynchronized pattern, • - higher metabolic rate and body temperature, • pupils become highly constricted (miosis), • rapid eye movements, • respiration is relativelyunresponsible to blood CO2, • reduced responses to heat and cold (amibent body temperature), • penile erections.

26. REM sleep sejttípusai non-REM-on cells- anterior hypothalamus - sleep generator REM-waking-on cells- brain stem reticular formation - active in waking and REM (excite motor neurons) PGO-on cells- pontine reticular formation REM-off cells- biogenic amine cells REM-on cells- pontine reticular formation - very active in REM stages

28. NREM – REM sleep cycle NREM 1-4 (70-80 min) NREM 3-2 (15-20 min) 90-110 min x 6/night REM (5-10 min) adults: 50-60% in NREM stage 2 REM sleep: 20-25% 15-20% in NREM stage 3+4 5 % in NREM stage 1

29. REM-off cells. Aminergic nuclei (green circles) diffusely project throughout much of the forebrain, regulating the activity of cortical and hypothalamic targets directly. Neurons of the tuberomammillary nucleus (TMN) contain histamine (HIST), neurons of the raphé nuclei contain 5-HT and neurons of the locus coeruleus (LC) contain noradrenaline (NA).

30. brain areas involved in sleep ascending reticulothalamic system (NREM) pontine-geniculo-occipital (PGO) axis (REM) circadian rhythm

31. Suprachiasmatic nucleus embedded in the upper surface of the optic chiasm in the hypothalamus. It participates in setting the normal sleep-wake cycle through connections with the pineal gland. Suprachiasmatic neurons works as an internal cirdadian pacemaker. It receives input from the retina (retino-hypothalamic tract). The suprachiasmatic nucleus regulates the timing of sleep, it is not responsible for sleep itself.

33. brain areas involved in sleep ascending reticulothalamic system (NREM) pontine-geniculo-occipital (PGO) axis (REM) circadian rhythm hypothalamic flip-flop switch ventrolateral preoptic nucleus

34. non-REM-on cells. Sleep-promoting neurons of the ventrolateral preoptic nucleus (VLPO, red circle) contain GABA and galanin (Gal). These cells produce sleep by inhibition histaminergic cells in the posterior hypothalamus and cells in the midbrain reticular formation.

36. The projections from the ventrolateral preoptic nucleus (VLPO) to the main components of the ascending arousal system and block their activity (non-REM-on cells).Axons from the VLPO directly innervate the cell bodies and proximal dendrites of neurons in the major monoamine arousal groups. Within the major cholinergic groups, axons from the VLPO mainly innervate interneurons, rather than the principal cholinergic cells. Abbreviations: LC, locus coeruleus; LDT, laterodorsal tegmental nuclei; PPT, pedunculopontine tegmental nuclei; TMN, tuberomammillary nucleus; VLPO, ventrolateral preoptic nucleus. The blue circle indicates neurons of the LDT and PPT; green circles indicate aminergic nuclei; and the red circle indicates the VLPO.

37. brain areas involved in sleep ascending reticulothalamic system (NREM) pontine-geniculo-occipital (PGO) axis (REM) circadian rhythm hypothalamic flip-flop switch ventrolateral preoptic nucleus tuberomamillary nucleus

38. Lesions of the posterior hypothalamic area may cause hypersomnolence or even coma. This area contains the tuberomammillary nucleus, housing hundreds of histaminergic neurons, which project widely to the gray matter of the brain and spinal cord. Histaminergic fibers destined for the cerebral cortex. They branch within the superficial layers of the frontal cortex, and run back to supply the cortex of the parietal, occipital, and temporal lobes. Tuberomammillary histaminerg neurons activate H1 receptors on cortical neurons. The tuberomammillary nucleus play an important role in the arousal mechanism, and activated during the awake state by orexin.

40. brain areas involved in sleep ascending reticulothalamic system (NREM) pontine-geniculo-occipital (PGO) axis (REM) circadian rhythm hypothalamic flip-flop switch ventrolateral preoptic nucleus tuberomamillary nucleus orexin (and MCH) neurons

41. Orexin neurons in the lateral hypothalamic area innervate all of the components of the ascending arousal system,as well as the cerebral cortex (CTX) itself. • Excitatory, they may help maintain wakefulness by increasing the activity of the ascending arousal system • Orexin neurons are wake-active • Orexin enurons might influence both sides of the flip-flop circuit by direct projections to both sides • Abbreviations: BF, basal forebrain cholinergic nuclei; LC, locus coeruleus; LDT, laterodorsal tegmental nuclei; PPT, pedunculopontine tegmental nuclei; TMN, tuberomammillary nucleus. Blue circles indicate cholinergic neurons of the BF, LDT and PPT; green circles indicate monoaminergic nuclei.

42. A model for reciprocal interactions between sleep- and wake-promoting brain regions, which produces aflip–flop switch. • Inhibitory pathways are shown in red, and the excitatory pathways in green. The blue circle indicates cholinerg neurons of the LDT and PPT; green boxes indicate aminergic nuclei; and the red box indicates the VLPO. • Aminergic regions such as the TMN, LC and DR promote wakefulness by direct excitatory effects on the cortex and by inhibition of sleep-promoting neurons of the VLPO. • During sleep, the VLPO inhibits amine-mediated arousal regions through GABAergic and galaninergic (GAL) projections. This inhibition of the amine-mediated arousal system disinhibits VLPO neurons, further stabilizing the production of sleep. • The extended VLPO (eVLPO) might promote REM sleep by disinhibiting the PPT–LDT; its axons innervate interneurons within the PPT–LDT, as well as aminergic neurons that normally inhibit REM-promoting cells in the PPT–LDT. • - Orexin/hypocretin neurons (ORX) in the lateral hypothalamic area (LHA) might further stabilize behavioral state by increasing the activity of aminergic neurons, thus maintaining consistent inhibition of sleep-promoting neurons in the VLPO and REM-promoting neurons in the PPT–LDT. • Abbreviations: DR, dorsal raphé nucleus; HIST, histamine; LC, locus coeruleus; LDT, laterodorsal tegmental nuclei; PPT, pedunculopontine tegmental nuclei; REM, rapid eye movement; TMN, tuberomammillary nucleus; VLPO, ventrolateral preoptic nucleus.

43. álom – dreams

44. The Sphinx at Giza showing the stone stela at its base telling how Thutmes IV listened to the god Hormokhu in adream.Thutmes IV cleared the sand covering the great Sphinx, as requested by Hormokhu, and was granted prosperity. Thutmes IV lived approximately 1450 B.C.

46. Dreaming Dreaming only in REM sleep Strong activation of the 1) anterior cingulate cortex (dream movement and emotion) 2) premotor areas 3) motor cortex (rapid eye movement, sleep-behavior) 4) basal ganglia (fictive motion of dreams) Reciprocal inhibition between frontal and limbic areas (inhibitory functions are deactivated) Prefrontal cortex deactivation → bizarreness of dreams

47. lesions lesions felébredés – kezdeményezés arousal – response initiation Prefrontal cortex: - initiation of goal-directed behavior delayed responses - attention distractibility (reduced ability to continuous attention and activity) - selection of specific behavior among several others

48. Spinoreticulothalamic tract „ascending reticular activating system” ① Elülső cingularis és dorsomedialis prefrontális kéreg ②Középső cingularis kéreg → akcióra irányított figyelem, megelőzés ② ①

49. dorsolateral prefrontal cortex • Emotional labeling of stimuli, goal-directed behavior, movement • Executive functions, logic planning

50. téli alvás