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Function of the midbrain, basal
ganglia and diencephalon
Prof. Romana Šlamberová, MD PhD
Department of Normal, Pathological and
Clinical Physiology
Midbrain (1)
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Mesencephalon (or midbrain)
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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:
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Functional connection between periphery and thalamus.
Its substantia nigra is closely associated with motor system
pathways of the basal ganglia.
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Dopamine produced in the substantia nigra plays a role in motivation and
habituation.
Midbrain (2)
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tectum (posterior)
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inferior colliculi - auditory
superior colliculi - vision
cerebral peduncle
(anterior)
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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
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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.
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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.
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projects to the medial geniculate nucleus of the thalamus and to the
primary auditory cortex.
Cerebral peduncle
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The cerebral peduncle - everything in the
mesencephalon except the tectum.
The region includes:
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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
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The tegmentum (from Latin for "covering") between the
substantia nigra and cerebral aqueduct
The crus cerebri - not considered part of the 'tegmentum‘
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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
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Ventral tegmental area (VTA)
Red Nucleus (nucleus ruber)
Periaqueductal gray (PAG)
VTA
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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
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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
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Function:
 motor coordination
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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
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PAG
the gray matter located around the cerebral aqueduct within the tegmentum of the midbrain
Function:
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Descending modulation of pain
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the ascending pain and temperature fibers of the spinothalamic tract also send
information to the PAG via the spinomesencephalic tract
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Role in analgesia
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Stimulation of the periaqueductal gray matter of the midbrain activates enkephalinreleasing neurons that project to the raphe nuclei in the brainstem
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Role in defensive behavior
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Experimental stimulation in animals – defensive behavior – freezing, running away,
tachycardia and increazed blood pressure
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Role in reproductive behavior
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Neurons of the PAG are excited by endorphins and by opiate analgesics.
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Role in maternal behavior
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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.
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Substantia nigra
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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
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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)
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The thalamus
(from Greek =
bedroom,
chamber)
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paired and
symmetric part of
the brain
main part of the
diencephalon
Thalamus (2)
Thalamus (3)
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dorsal thalamus - 15 nuclei
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ventral thalamus (the thalamic reticular nucleus – the
major one)
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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
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Specific functions
Connection to sensory organs
Well bounded
Nuclei:
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Corpus geniculatum laterale – visual
 Fibers from tractus opticus and colliculus superior
 Fibers to radiatio optica and visual cortex
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Corpus geniculatum mediale – auditory
 Fibers from colliculus inferior
 Fibers to auditory cortex
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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
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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
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Function:
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Regulation of motor function
Ncl. ventralis lateralis
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from BG and cerebellum
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to gyrus precentralis (Brodmann areas 4 and 6)
Association nuclei
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Integration function
from senses (eyes, ears, skin) - polymodal afferentation (from more places)
to association cortex
Nuclei:
 Ncl. medialis dorsalis
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Ncl. Anterior
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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
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in-between association and non-specific nuclei
Integration of intrathalamic functions (connections of thalamic nuclei)
Also connection with BG, cerebellum, cortex
Pineal gland
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Also called pineal body, epiphysis cerebri,
epiphysis, conarium or the "third eye“
Function:
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Endocrine – secretion of melatonin
(derivate of serotonin)
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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
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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
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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)
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Infradian rhythms - cycles longer than a day
 the annual migration or reproduction cycles or the human menstrual cycle
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Ultradian rhythms - cycles shorter than 24 hours
 Sleeping cycle, 3-hour cycle of growth hormone production, other
hormones
Chronobiology 2
Circadian rhythms
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Circadian clock located in the
Suprachiasmatic nucleus
The SCN sends information to
other hypothalamic nuclei and
the pineal gland
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to modulate body temperature
production of hormones - cortisol
and melatonin
Secretion of melatonin peaks at
night.
Jet lag
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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:
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Sleeping problems, irritation, cognition problems, problems with concentration, GIT
problems
Basal ganglia (1)
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Important deap nuclei
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Functions:
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Belong to telecephalon
Connected with the cerebral cortex, thalamus and brainstem.
motor control
cognition
emotions
Parts:
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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
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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
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Ventral striatum:
 NAc
 olfactory tubercle
Function:
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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
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Dorsal striatum:
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Connected to the substantia nigra and globus pallidus.
Function:
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Putamen
Caudate nucleus
Regulation of movements
Cognition
Plays a role in degenerative neurological disorders, such as Parkinson's
disease
Neurotransmitters:
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Dopamine (main)
also GABA and substance P
Caudate nucleus
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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:
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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)
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Parts:
 Lateral pallidum (GPe)
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Medial pallidum (GPi)
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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:
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regulation of voluntary movement
Subthalamic
nucleus
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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
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Dopamine = Catecholamine
 can be supplied as a medication that acts on
the sympathetic nervous system (increased
heart rate and blood pressure)
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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
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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.
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Movement
Cognition
Regulating prolactin secretion
Motivation and pleasure (food, sex, drugs)
Disruption to the dopamine system
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Parkinson’s disease, schizophrenia, psychosis, depression
Serotonin
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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:
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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
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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)
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Parkinson's disease is a degenerative disorder of
the CNS that impairs the motor skills and speech.
It is characterized by:
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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)
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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
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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