Transcript Az alvás és ébrenlét, gondolkodás, morális és emocionális

Funkcionális neuroanatómia
12.
Az alvás és ébrenlét, aktiválódás, figyelem
és az elhatározás neuroanatómiája
2012 - Neuromorfológia PhD program
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.
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.
Reticular formation
mesencephalic reticular formation
promotes the walking state
medullary reticular formation
inhibits the walking state
(sleep induction)
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.
ébrenlét
wakefulness
Spinoreticulothalamic tract
A thalamus intralaminaris magjaiból eredő
thalamo-corticalis rostok számos kérgi
területen végződnek: a prefrontalis kéregben,
az elülső cinguláris kéregben, a premotoros
areában, az insularis kéregben és a parietális
asszociációs area neuronjain.
„ascending reticular activating system”
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).
Cholinerg sejtcsoportok
medial septal
nucleus of the diagonal band
nucleus basalis (Meynert)
laterodorsal tegmental nucleus
pedunculopontine nucleus
Ch1
Ch2-Ch3
Ch4
Ch5
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.
sleep
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
brain areas involved in sleep
ascending reticulothalamic system (NREM)
slow-wave sleep
NREM sleep
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).
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.
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
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
NREM sleep EEG hullámai
REM sleep
brain areas involved in sleep
ascending reticulothalamic system (NREM)
pontine-geniculo-occipital (PGO) axis (REM)
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 relatively unresponsible to blood CO2,
- reduced responses to heat and cold (amibent body temperature),
- penile erections.
REM sleep sejttípusai
non-REM-on cells
REM-waking-on cells
- anterior hypothalamus
- brain stem reticular formation
-
sleep generator
active in waking and REM
(excite motor neurons)
PGO-on cells
REM-off cells
REM-on cells
- pontine reticular formation
- biogenic amine cells
- pontine reticular formation
-
very active in REM stages
NREM – REM sleep cycle
NREM 1-4
NREM 3-2
REM
(70-80 min)
(15-20 min)
(5-10 min)
90-110 min x 6/night
adults: 50-60% in NREM stage 2
15-20% in NREM stage 3+4
5 % in NREM stage 1
REM sleep: 20-25%
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).
brain areas involved in sleep
ascending reticulothalamic system (NREM)
pontine-geniculo-occipital (PGO) axis (REM)
circadian rhythm
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 (retinohypothalamic tract).
The suprachiasmatic nucleus regulates the timing of sleep, it
is not responsible for sleep itself.
brain areas involved in sleep
ascending reticulothalamic system (NREM)
pontine-geniculo-occipital (PGO) axis (REM)
circadian rhythm
hypothalamic flip-flop switch
ventrolateral preoptic nucleus
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.
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.
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
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.
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
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.
A model for reciprocal interactions between sleep- and
wake-promoting brain regions, which produces a flip–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.
álom – dreams
The Sphinx at Giza showing the stone stela at its base telling how
Thutmes IV listened to the god Hormokhu in a dream. Thutmes IV
cleared the sand covering the great Sphinx, as requested by Hormokhu,
and was granted prosperity. Thutmes IV lived approximately 1450 B.C.
Dreaming
Dreaming only in REM sleep
Strong activation of the
1) anterior cingulate cortex
2) premotor areas
3) motor cortex
4) basal ganglia
(dream movement and emotion)
(rapid eye movement, sleep-behavior)
(fictive motion of dreams)
Reciprocal inhibition between frontal and limbic areas (inhibitory functions
are deactivated)
Prefrontal cortex deactivation → bizarreness of dreams
felébredés – kezdeményezés
arousal – response initiation
Prefrontal cortex:
- initiation of goal-directed behavior lesions delayed responses
- attention lesions distractibility (reduced ability to continuous
attention and activity)
- selection of specific behavior among several others
Spinoreticulothalamic tract
„ascending reticular activating system”
① Elülső cingularis és
dorsomedialis prefrontális kéreg
② Középső cingularis kéreg →
akcióra irányított figyelem,
megelőzés
②
①
dorsolateral prefrontal cortex
• Emotional labeling of stimuli, goaldirected behavior, movement
• Executive functions, logic planning
téli alvás
c-Fos expression in the preoptic area during hibernation.
In ART, low level of c-fos expression was detected in
neurons throughout the entire preoptic area (B), while in
ET the ventrolateral subdivision of the preoptic area
exhibited stronger c-fos expression (C). In animals during
torpor (LT) the area remained silent (D). During arousal
(EA and LA) we found activity in the ventromedial
subdivision of the preoptic area (E,F), and in IBA animals,
strong c-fos activity was detected all throughout the area
(G).
c-Fos expression in the suprachiasmatic nucleus during
hibernation.
The SCN showed low activity in ART (B), while during
torpor, c-fos expression in the neurons of the SCN
became progressively stronger (C–E) peaking in EA (E)
and returning to lower levels of expression in LA (F) and
IBA (G).
c-Fos expression in the reticular thalamic nucleus and the
somatomotor cortex during hibernation.
The reticular thalamic nucleus showed no activity in
awake animals (ART and IBA) (B,D), meanwhile during
the torpor phase of the hibernation bout (LT), strong c-fos
expression was detected in the nucleus (C).
In contrast, activated neurons were found in the
somatomotor cortex in only awake animals (ART and
IBA) (E,G), but not during torpor (LT) (F).
c-Fos expression in the paraventricular nucleus during
hibernation.
The PVN showed no c-fos activity in ART (B), in ET (C),
and in LT (D); however, in IBA strong c-fos expression
was detected mainly in the parvocellular neurons of the
nucleus (E).
c-Fos expression in the choroid plexus and the
ependymal cells of the lateral ventricle during
hibernation.
Neither the epithelial cells of the choroid plexus nor the
ependymal cells of the lateral ventricle showed any c-fos
expression in awake animals (ART and IBA) (B,G).
During torpor, we detected increasing c-fos expression in
the choroid plexus, starting in ET (C), peaking in EA (E),
and diminishing in LA (F), while the ependymal cells of
the lateral ventricle exhibited activity only in the arousal
phases (EA and LA) (E,F).
c-Fos expression in tanycytes and the ependymal cells of
the third ventricle during hibernation.
No c-fos activity was detected in ART (B) and ET (C)
phases. Strong c-fos expression was observed in both
tanycytes and third ventricular ependymal cells during LT
(D) and EA (E), while this activity diminished in LA (F).
Interestingly, neurons in the arcuate nucleus and in the
dorsomedial hypothalamus exhibited strong activity in
IBA (G).
Formatio reticularis
Az agytörzs integráló rendszere, ahol számos agyterületről (cortex,
cerebellum, törzsdúcok, gerincvelő) érkező információ feldolgozása történik.
Számos reflex (légzés, keringés, alvás) és projekciós pályarendszer útján a
kérgi tevékenységek aktiválásával („felszálló reticuláris aktiváló rendszer”),
agytörzsi autonóm központok, továbbá az izomtónus reakciókészségének
emelésével az adekvát szomatikus válaszok kidolgozásáért és
megvalósításáért felelős neuronok összessége.
Nucleus pedunculopontinus
A középagy és a híd határán, a colliculus inferiortól ventrálisan, a
tegmentumban levő mag, mely magába foglal egy cholinerg sejtcsoportot
(Ch6) is, mely a thalamus beidegzésében vesz részt. Szerepet
tulajdonítanak neki a fázisos REM („rapid-eye-movement”) alvásban.
Közvetlen rostokat kap a törzsdúcokból és a kisagyból. Részben átfed a
„középagyi motoros régió” („mesencephalic locomotor region”) területével. A
reticulospinalis pályához küld rostokat. A járás folyamatosságának
fenntartásában van szerepe. Sérülése, illetve a törzsdúcokkal való
kapcsolatának megszakadása lehet felelős a Parkinson-kórra jellemző
járási zavaroknak és rigiditásnak.
Nucleus reticularis thalami
Vékony, C-alakú mag, mely körbeveszi a thalamus felső és oldalsó részét,
valamint elülső pólusát. Sejtjei a thalamus külső lemeze és a capsula
interna között helyezkednek el. Számos axon-kollaterálist kap a corticothalamikus pályákon át szinte valamennyi kérgi areából. Kétirányú
kapcsolatban van az elülső magcsoport kivételével a thalamus összes
magjával, a törzsdúcokkal és a formatio reticularisszal. Sejtjei GABAerg
gátló neuronok, s bár nincs közvetlen projekciója a kéregbe, a thalamusmagok gátlásával szinte egy funkcionális gát szerepét tölti be a thalamocorticális kapcsolatokban.
Nucleus suprachiasmaticus
A hypothalamus elülső részében, a harmadik agykamra két oldalán alul,
közvetlenül a chiasma opticum felett helyezkedik el. A napszaki ritmus
fenntartásában van szerepe. „Biológiai órá”-nak nevezik – bár helyesebb
lenne pacemaker-nek hivni. Rostokat kap a retinából (tractus retinohypothalamicus), valamint a corpus geniculatum lateralis speciális
sejtcsoportjából és a középagyi raphe magoktól. A nucleus
suprachiasmaticus rostokat küld a hypothalamus paraventriculáris
magjához, a thalamushoz, a törzsdúcokhoz és multiszinaptikus pályákon át
a locus coeruleushoz (alvás-ébrenlét szabályozása) és a corpus pinealéhoz
(melatonin szintézis).
Regio preoptica – area preoptica
A hypothalamus elülső része, a commissura anterior kereszteződése előtti
és alatti terület. Közvetlen idegi kapcsolatban van a hippocampusszal
(„precommissuralis fornix rostok”) és az amygdalával. Sejtjeinek egy része
gonadotropin-releasing hormont termel, és az eminentia medianába
projíciál. A régió mediális magjának (nucleus preopticus medialis) egyik
szubdivíziója a szexuális dimorfizmus központja. A régióban helyezkedik el
az agy thermoregulációs központja, valamint a terület ventrolaterális
részében találhatók az alvás mechanizmusában szerepet vivő GABAerg
neuronok (VLPO).
Retino-hypothalamikus pálya
A retina ganglionsejtjeiből eredő pálya. Rostjai a nervus opticuson belül
futnak, a koponyaüregbe való belépés után a chiasma opticumban
kereszteződnek és zömmel a nucleus suprachiasmaticusban végződnek.