Transcript Function
Function of the midbrain, basal
ganglia and diencephalon
Prof. Romana Šlamberová, MD PhD
Department of Normal, Pathological and
Clinical Physiology
Midbrain (1)
Mesencephalon (or midbrain)
name due to the development - the middle of three vesicles
that arise from the neural tube that forms the brain of developing
animals.
Caudally from the diencephalon and rostrally from the
pons.
The mesencephalon is considered part of the brain stem.
Function:
Functional connection between periphery and thalamus.
Its substantia nigra is closely associated with motor system
pathways of the basal ganglia.
Dopamine produced in the substantia nigra plays a role in motivation and
habituation.
Midbrain (2)
tectum (posterior)
inferior colliculi - auditory
superior colliculi - vision
cerebral peduncle
(anterior)
midbrain tegmentum
crus cerebri
substantia nigra
As a mnemonic the mesencephalic cross-section resembles a bear (or teddybear)
upside down with the two red nuclei as the eyes and the crus cerebri as the ears.
Tectum
The tectum (Latin: roof) has two parts – superior and
inferior colliculi = corpora quadrigemina.
The superior colliculus - involved in visual processing, and
control of saccadic eye movements and eye-head movements –
light stimulus.
projects to lateral geniculate nucleus of the thalamus and then to the
primary visual cortex.
The inferior colliculus - involved in auditory processing and
head-ear movements – sound stimulus.
projects to the medial geniculate nucleus of the thalamus and to the
primary auditory cortex.
Cerebral peduncle
The cerebral peduncle - everything in the
mesencephalon except the tectum.
The region includes:
midbrain tegmentum
crus cerebri
substantia nigra
pretectum
Nerve tracts from motor areas of the brain - to the
cerebral peduncle and then to thalamic nuclei.
Tegmentum
The tegmentum (from Latin for "covering") between the
substantia nigra and cerebral aqueduct
The crus cerebri - not considered part of the 'tegmentum‘
not part of the primitive neural tube, but grew as projections from the
cerebral cortex.
Parts that were inside the primitive neural tube and remained
an integral part of it after complete development (e.g. the red
nucleus) are considered part of the tegmentum.
Pertinent areas of Tegmentum
Ventral tegmental area (VTA)
Red Nucleus (nucleus ruber)
Periaqueductal gray (PAG)
VTA
close to the substantia nigra and the red nucleus.
rich in dopamine and serotonin neurons
part of two major dopamine pathways:
the mesolimbic pathway - connects the VTA and the nucleus
accumbens
the mesocortical pathway - connects the VTA to cortical areas in
the frontal lobes
Function
part of the pleasure system, or reward circuit
Psychostimulant drugs (such as cocaine) directly target VTA
one of the major sources of incentive and behavioral motivation
emotion and security motivation (avoidance and fear-conditioning)
Mesolimbic reward circuit
Mesolimbic
(cortico-striatal)
reward circuit
[from (Everitt and
Robbins, 2005)].
PFC = Prefrontal
cortex; BLA =
balateral nucleus of
the amygdala; CeA =
central nucleus of the
amygdala; NAc =
nucleus accumbens;
VTA = ventral
tegmental area; SNc =
substantia nigra pars
compacta; VGP =
ventral globus
pallidus; DGP = dorzal
globus pallidus.
Colors = neuromediator systems: orange = glutamatergic; blue =
dopaminergic; green = GABAergic.
Red nucleus
Function:
motor coordination
Rubrospinal tract – extrapyramidal
pathway (less important in humans than
in many other mammals - in humans
the corticospinal tract is dominant).
Control of crawling of babies
Controls the muscles of the shoulder
and upper arm (but lower arm and
hand as well).
Control of arm-swinging in normal
walking
The rubrospinal projection:
receives many inputs from the contralateral cerebellum and an input
from the ipsilateral motor cortex
sends efferent axons to the contralateral half of the spinal cord
PAG
the gray matter located around the cerebral aqueduct within the tegmentum of the midbrain
Function:
Descending modulation of pain
the ascending pain and temperature fibers of the spinothalamic tract also send
information to the PAG via the spinomesencephalic tract
Role in analgesia
Stimulation of the periaqueductal gray matter of the midbrain activates enkephalinreleasing neurons that project to the raphe nuclei in the brainstem
Role in defensive behavior
Experimental stimulation in animals – defensive behavior – freezing, running away,
tachycardia and increazed blood pressure
Role in reproductive behavior
Neurons of the PAG are excited by endorphins and by opiate analgesics.
Role in maternal behavior
The PAG contains a high density of vasopressin and oxytocin receptors, and it has direct
connections with the orbitofrontal cortex, which might mediate the role of the PAG in
maternal love.
Substantia nigra
The substantia nigra, (Latin for "black substance")
Function:
dopamine production in the brain (vital role in reward and addiction)
Motor control
It consists of two strongly contrasted ensembles:
pars compacta - contains neurons - colored black (black stripes) by
the pigment neuromelanin
pars reticulata – dendrites from pars compacta neurons
Dopamine is synthesized in the dopaminergic neurons (substantia nigra
pars compacta)
Disruption - serious motor and cognitive deficits (Parkinson's
disease)
Diencephalon
situated between the cerebrum
and the brain stem
Parts:
the thalamus
the subthalamus - STN
the hypothalamus – part of the
limbic system
the epithalamus – pineal gland
Thalamus (1)
The thalamus
(from Greek =
bedroom,
chamber)
paired and
symmetric part of
the brain
main part of the
diencephalon
Thalamus (2)
Thalamus (3)
dorsal thalamus - 15 nuclei
ventral thalamus (the thalamic reticular nucleus – the
major one)
cells project to the cerebral cortex
reticular cells (GABAergic) project into the dorsal thalamus to inhibit
relay cells
Function:
to gate and modulate the flow of information to cortex
sensory systems auditory, somatic, visceral, gustatory and
visual systems
"motor" systems
regulating states of sleep and wakefulness
Specific nuclei
Specific functions
Connection to sensory organs
Well bounded
Nuclei:
Corpus geniculatum laterale – visual
Fibers from tractus opticus and colliculus superior
Fibers to radiatio optica and visual cortex
Corpus geniculatum mediale – auditory
Fibers from colliculus inferior
Fibers to auditory cortex
Ventrobasal complex – somatosensory - going to gyrus postcentralis
Ncl. ventroposterolateralis - from somatosensory and skin receptors
of the body
Ncl. ventroposteromedialis – from somatosensory and skin receptors
of the face
Non-specific sensoric nuclei
Unspecific function
part of ascending tracts from RF
going to frontal and prefrontal cortex (Brodmann areas 4, 6, 9)
Nuclei:
Ncl. centralis lateralis
Ncl. centralis medialis
Ncl. Parafascicularis
Ncl. habenularis
Important for pain information (visceral pain)
When stimulating - recruiting response (desynchronization – beta
activity 15-30 Hz)
Motor nuclei
Function:
Regulation of motor function
Ncl. ventralis lateralis
from BG and cerebellum
to gyrus precentralis (Brodmann areas 4 and 6)
Association nuclei
Integration function
from senses (eyes, ears, skin) - polymodal afferentation (from more places)
to association cortex
Nuclei:
Ncl. medialis dorsalis
Ncl. Anterior
inputs from the amygdala and olfactory cortex
projects to the prefrontal cortex and the limbic system
role in attention, planning, organization, abstract thinking, multi-tasking, and active
memory
Inputs from the mammillary bodies via the mammillothalamic tract and from the
subiculum via the fornix
projects to the cingulate gyrus
role in the modulation of alertness and are involved in learning and memory
Ncl. reticularis thalami
in-between association and non-specific nuclei
Integration of intrathalamic functions (connections of thalamic nuclei)
Also connection with BG, cerebellum, cortex
Pineal gland
Also called pineal body, epiphysis cerebri,
epiphysis, conarium or the "third eye“
Function:
Endocrine – secretion of melatonin
(derivate of serotonin)
Hormone that affects the modulation of
wake/sleep patterns and seasonal
functions
The name - Dermatology professor Aaron
B. Lerner from Yale University in 1958,
hopped that a substance from the pineal
might be useful in treating skin diseases
(wrong)
In animals, the pineal gland appears to
play a major role in sexual development,
hibernation, metabolism, and seasonal
breeding
Chronobiology 1
Greek chrónos = "time"
a field of biology that examines periodic (cyclic) phenomena in living organisms
and their adaptation to solar- and lunar-related rhythms - biological rhythms
Circadian rhythms - about 24 hrs (25 hrs)
Diurnal - organisms active during daytime
Nocturnal - organisms active in the night
Crepuscular - animals primarily active during the dawn and dusk hours
(white-tailed deer, some bats)
Infradian rhythms - cycles longer than a day
the annual migration or reproduction cycles or the human menstrual cycle
Ultradian rhythms - cycles shorter than 24 hours
Sleeping cycle, 3-hour cycle of growth hormone production, other
hormones
Chronobiology 2
Circadian rhythms
Circadian clock located in the
Suprachiasmatic nucleus
The SCN sends information to
other hypothalamic nuclei and
the pineal gland
to modulate body temperature
production of hormones - cortisol
and melatonin
Secretion of melatonin peaks at
night.
Jet lag
medically referred to as desynchronosis
a physiological condition which results from alterations to the body's
circadian rhythms resulting from rapid long-distance transmeridian travel on
a (typically jet) aircraft.
The speed at which the body adjusts to the new schedule depends on the
individual
Worst from west to east
Symptoms:
Sleeping problems, irritation, cognition problems, problems with concentration, GIT
problems
Basal ganglia (1)
Important deap nuclei
Functions:
Belong to telecephalon
Connected with the cerebral cortex, thalamus and brainstem.
motor control
cognition
emotions
Parts:
the striatum (putamen, caudate nucleus, nucleus accumbens)
globus pallidus (internal and external segments)
subthalamic nucleus (STN)
substantia nigra (SN) - compacta (SNc), reticulata (SNr)
Basal ganglia (2)
Basal ganglia (3)
Striatum
Function:
planning and modulation of
movement
cognitive processes involving
executive function
reward, but also by aversive
circuits
Pathology:
loss of dopaminergic
innervation to the striatum
(and other basal ganglia) from
SN = Parkinson's disease
lesion of the striatum - the
Huntington disease, choreas,
choreoathetosis and
dyskinesias
Nucleus accumbens
– ventral striatum
Ventral striatum:
NAc
olfactory tubercle
Function:
role in reward, laughter, pleasure, addiction, fear, and the placebo effect
2 parts: core and
shell
Types of neurons:
95% of GABAergic
Rest
cholinergic
interneurons
Putamen
Dorsal striatum:
Connected to the substantia nigra and globus pallidus.
Function:
Putamen
Caudate nucleus
Regulation of movements
Cognition
Plays a role in degenerative neurological disorders, such as Parkinson's
disease
Neurotransmitters:
Dopamine (main)
also GABA and substance P
Caudate nucleus
C-shape structure with a wider head at the front, tapering to a
body and a tail.
highly innervated by dopamine neurons (from VTA and SNc)
Function:
Learning and memory (feedback processing)
Language comprehension (left caudate)
Threshold control (? measuring the general activity of cerebral cortex
and controlling the threshold potential – excitation ?)
Role in human love (fMRI – falling in love – also VTA)
Role in Obsessive compulsive disorder
Globus pallidus (pallidum)
Parts:
Lateral pallidum (GPe)
Medial pallidum (GPi)
receives a strong glutamatergic
projection from the subthalamic
nucleus
sends GABAergic axons to other
parts of basal ganglia
receives a strong glutamatergic
projection from other parts of
basal ganglia
sends GABAergic axons to the
thalamus
Function:
regulation of voluntary movement
Subthalamic
nucleus
small lens-shaped nucleus
Function:
Control of movement
Together with SN (ending of seizures in epilepsy)
The chronic stimulation of the nucleus leads to a clear
improvement of Parkinsonian symptoms.
Unilateral destruction or disruption of the subthalamic
nucleus – produces hemiballismus (a movement disorder,
characterised by unilateral wild, large amplitude flinging
movements of the arm and leg, normally causing falls and
preventing postural maintenance.)
Dopamine
Dopamine = Catecholamine
can be supplied as a medication that acts on
the sympathetic nervous system (increased
heart rate and blood pressure)
cannot cross the blood-brain barrier - L-DOPA
(levodopa) = the precursor)
dopamine receptor - D1, D2, D3, D4 and D5,
and their variants
produced in several areas of the brain, including
the substantia nigra
also a neurohormone released by the
hypothalamus
inhibits the release of prolactin from the
anterior lobe of the pituitary
Function of dopamine
Dopamine is crucial to the reward system.
In nature, we learn to repeat behaviors that lead to unexpected
rewards. Dopamine is therefore believed by many to provide a
teaching signal to parts of the brain responsible for acquiring
new motor sequences, i.e., behaviors.
Movement
Cognition
Regulating prolactin secretion
Motivation and pleasure (food, sex, drugs)
Disruption to the dopamine system
Parkinson’s disease, schizophrenia, psychosis, depression
Serotonin
Serotonin (5-hydroxytryptamine, or 5-HT) is
a monoamine neurotransmitter synthesized in
serotonergic neurons in the CNS (also in GIT).
Function: regulation of anger, aggression, body
temperature, mood, sleep, vomiting, sexuality,
and appetite.
Disorders:
Psychiatry diseases - increase in aggressive and angry
behaviors, clinical depression, obsessive-compulsive
disorder, migraine, irritable bowel syndrome, tinnitus,
fibromyalgia, bipolar disorder, and anxiety disorders.
Extremely high levels of serotonin – toxic effects
causing serotonin syndrome.
In practice it may be caused by an overdose
of a single anti-depressant drug.
Selective serotonin re-uptake inhibitors
= SSRIs - treatment of depression, anxiety
disorders, and some personality disorders
Serotonin syndrome
Mild symptoms
increased heart rate, shivering, sweating, dilated pupils, myoclonus
(intermittent tremor or twitching), as well as overresponsive reflexes
Moderate intoxication
hyperactive bowel sounds, high blood pressure and hyperthermia; a
temperature as high as 40 °C; mental changes - hypervigilance and
agitation.[
Severe symptoms
severe increase in heart rate and blood pressure (lead to shock);
temperature may rise to above 41 °C; metabolic acidosis,
rhabdomyolysis, seizures, renal failure, and disseminated intravascular
coagulation.
Parkinson's disease (1)
Parkinson's disease is a degenerative disorder of
the CNS that impairs the motor skills and speech.
It is characterized by:
Change in facial expression (staring, lack of blinking) –
Poker face
Failure to swing arm when walking
Flexion (stooped) posture
"Frozen" painful shoulder
Limping or dragging of leg
Changes in sensation - numbness, tingling, achiness or
discomfort of the neck or limbs
Softness of the voice
Subjective sensation of internal trembling Resting tremor
Parkinson's disease (2)
Mnemonic device
T - Tremor - Involuntary trembling of the
limbs (resting tremor)
R - Rigidity - Stiffness of the muscles
A - Akinesia - Lack of movement or slowness
in initiating and maintaining movement
P - Postural instability - Characteristic bending
or flexion of the body, associated with
difficulty in balance and disturbances in gait
Parkinson's disease (2)
Dopaminergic
pathways of the
human brain in normal
condition (left) and
Parkinson's disease
(right).
Red Arrows indicate
suppression of the
target, blue arrows
indicate stimulation of
target structure.
Huntington's disease
most obvious symptoms are abnormal body
movements called chorea and a lack of coordination.
but it also affects a number of mental abilities and
some aspects of personality.
Chorea is characterized by brief, irregular
contractions that are not repetitive or rhythmic, but
appear to flow from one muscle to the next.
genetic disorder, symptoms commonly become
noticeable in a person's 40’s.
Degeneration in basal ganglias (striatum-CPu, cortex)
Huntington's disease