Transcript Synaptic receptors, neurotransmitters and brain modulators

Function of the midbrain, basal
ganglia and thalamus
Romana Šlamberová, MD PhD
Department of Normal,
Pathological and Clinical
Physiology
Introduction
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Slides from the lecture.
Respecting the copyrights it was not
possible to publish pictures showed at the
lecture at our website.
© 2007, Romana Slamberova, MD PhD
Midbrain (1)
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Mesencephalon (or midbrain) is the middle of three
vesicles that arise from the neural tube that forms the
brain of developing animals.
Caudally the mesencephalon adjoins the pons and rostrally
it
The mesencephalon is considered part of the brain stem.
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 of species from humans to the
most elementary animals such as insects.
Midbrain (2)
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tectum
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inferior colliculi
superior colliculi
cerebral peduncle
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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.
Midbrain (3)
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On the posterior (back) surface are located the
superior colliculus and the inferior colliculus.
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On the anterior surface the cerebral peduncles are
prominent.
These contain
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The superior colliculus - involved with saccadic eye
movements
The inferior colliculus - a synapsing point for sound
information
the corticospinal tract fibres (from the internal capsule)
the substantia nigra
Between the peduncles is the interpeduncular
fossa, which is a cistern filled with cerebrospinal fluid.
Tectum
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The tectum (Latin: roof) is the dorsal part of the midbrain and
has two parts – superior and inferior colliculi that form the
eminences of the corpora quadrigemina.
The superior colliculus is involved in preliminary visual
processing, and control of eye movements. It projects to lateral
geniculate nucleus of the thalamus.
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The superior colliculus (SC) is involved in the generation of saccadic eye
movements and eye-head coordination. The SC can also mediate some
oculomotor movements without cortical involvement.
The inferior colliculus is involved in auditory processing. It
receives input from various brainstem nuclei and projects to the
medial geniculate nucleus of the thalamus, which relays
auditory information to the primary auditory cortex.
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The inferior colliculus is the principal midbrain nucleus of the auditory
pathway and receives input from several more peripheral brainstem
nuclei in the auditory pathway, as well as inputs from the auditory
cortex.
Cerebral peduncle
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The cerebral peduncle, by most classifications, is
everything in the mesencephalon except the tectum.
The region includes:
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midbrain tegmentum
crus cerebri
substantia nigra
pretectum.
The peduncles are also known as the crus cerebri.
There are numerous nerve tracts from motor areas of
the brain project to the cerebral peduncle and then
project to various thalamic nuclei.
Tegmentum
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The tegmentum (from Latin for "covering") is the part of the
midbrain extending from the substantia nigra to the cerebral
aqueduct in a horizontal section of the midbrain and forms the
floor of the midbrain which surrounds the cerebral aqueduct.
Structures that have developed to grow ventral or lateral
outside this primitive tube as add-ons(e.g. the crus cerebri
in the anterior of the midbrain) are not considered part of the
'tegmentum' as they were 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
Red Nucleus
Ventral tegmental area
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Part of the midbrain, lying close to the substantia nigra and the red
nucleus.
It is rich in dopamine and serotonin neurons, and is part of two
major dopamine pathways:
 the mesolimbic pathway, which connects the VTA to the nucleus
accumbens
 the mesocortical pathway, which connects the VTA to cortical
areas in the frontal lobes.
Function - The ventral tegmentum is considered to be part of the
pleasure system, or reward circuit, one of the major sources of
incentive and behavioural motivation.
psychostimulant drugs (such as cocaine) directly target VTA. Hence,
it is widely implicated in neurobiological theories of addiction.
It is also shown to process various types of emotion and security
motivation, where it may also play a role in avoidance and fearconditioning.
Red nucleus
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The red nucleus (nucleus ruber) is a structure in the rostral
midbrain involved in motor coordination.
The red nucleus mainly controls the muscles of the shoulder
and upper arm, but it has some control over the lower arm and
hand as well. It is less important in its motor functions for
humans than in many other mammals, because, in humans, the
corticospinal tract is dominant.
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However the crawling of babies is controlled by the red
nucleus, as is arm-swinging in normal walking.
The rubrospinal projection: The red nucleus receives many
inputs from the contralateral cerebellum and an input from the
ipsilateral motor cortex, and sends efferent axons to the
contralateral half of the spinal cord.
Substantia nigra (1)
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The substantia nigra, (Latin for "black substance")
is a heterogeneous portion of the midbrain.
The substantia nigra is responsible for dopamine
production in the brain, and therefore plays a vital
role in reward and addiction.
It consists of two strongly contrasted ensembles:
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pars compacta - contains neurons which are coloured
black (black stripes) by the pigment neuromelanin that
increases with age
pars reticulata – dendrites from pars compacta neurons
Substantia nigra (2)
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Dopamine is biosynthesized in the dopaminergic neurons,
primarily in the substantia nigra pars compacta.
Disruption in the biosynthesis or transmission of dopamine can
lead to serious motor and cognitive deficits, such as
occurs in Parkinson's disease.
The neurons of the pars reticulata are fast-spiking pacemakers,
generating action potentials in the absence of synaptic input.
The pars reticulata is one of the two primary output nuclei of
the basal ganglia system (next to Pallidum) to the motor
thalamus.
The function of the neurons of the pars reticulata is profoundly
changed in parkinsonism and epilepsy.
Basal ganglia (1)
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The basal ganglia are important to life nuclei in the
brain interconnected with the cerebral cortex,
thalamus and brainstem.
Basal ganglia are associated with a variety of
functions: motor control, cognition, emotions and
learning.
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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The striatum is a subcortical part of the telencephalon.
It is a major part of the basal ganglia system: its input station.
Function:
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planning and modulation of movement pathways
involved in a variety of other cognitive processes involving executive
function
is activated by stimuli associated with reward, but also by aversive,
novel, unexpected or intense stimuli
Pathology:
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Parkinson's disease results in loss of dopaminergic innervation to the
striatum (and other basal ganglia)
The lesion of the striatum is also involved in the Huntington disease,
choreas, choreoathetosis and dyskinesias.
Globus pallidus (pallidum)
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The globus pallidus is a subcortical structure of the
brain.
It is a major element of the basal ganglia system.
Parts:
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Lateral pallidum (GPe): receives a strong glutamatergic
projection from the subthalamic nucleus. Sends GABAergic
axons to other parts of basal ganglia.
Medial pallidum (GPi): receives a strong glutamatergic
projection from other parts of Basal ganglia. Sends
GABAergic axons to the thalamus.
Subthalamic nucleus
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The subthalamic nucleus is a small lens-shaped
nucleus in the brain.
It is a part of the basal ganglia system.
The chronic stimulation of the nucleus leads to a
clear improvement of Parkinsonian symptoms.
Unilateral destruction or disruption of the
subthalamic nucleus – which can commonly occur via
a small vessel stroke in patients with diabetes,
hypertension, or a history of smoking – 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.)
Thalamus (1)
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The thalamus
(from Greek =
bedroom,
chamber) is a
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pair and
symmetric part of
the brain.
It constitutes the
main part of the
diencephalon.
Thalamus (2)
Thalamus (3)
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dorsal thalamus, which is comprised of roughly 15 nuclei
with relay cells that project to the cerebral cortex.
ventral thalamus (the major portion of which is the thalamic
reticular nucleus) - reticular cells are GABAergic and project
into the dorsal thalamus to inhibit relay cells.
Function:
 to gate and otherwise modulate the flow of information to
cortex.
 plays an important role in regulating states of sleep and
wakefulness.
 sensory systems auditory, somatic, visceral, gustatory and
visual systems
 "motor" systems
Dopamine (1)
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dopamine works as a neurotransmitter in the
CNS
dopamine receptor - D1, D2, D3, D4 and D5,
and their variants
Dopamine is produced in several areas of the
brain, including the substantia nigra.
Dopamine is also a neurohormone released by
the hypothalamus. Its main function as a
hormone is to inhibit the release of prolactin
from the anterior lobe of the pituitary.
Dopamine (2)
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Dopamine can be supplied as a medication that
acts on the sympathetic nervous system, producing
effects such as increased heart rate and blood
pressure.
Since dopamine cannot cross the blood-brain barrier,
dopamine given as a drug does not directly affect
the CNS.
To increase the amount of dopamine in the brains of
patients with diseases such as Parkinson's disease
and Dopa-Responsive Dystonia, L-DOPA (levodopa),
(the precursor), can be given because it can cross
the blood-brain barrier.
Function of dopamine
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Dopamine is central to the reward system. Dopamine
neurons are activated when an unexpected reward is
presented. 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: 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 can have toxic and
potentially fatal effects, causing a condition known as serotonin
syndrome. In practice, such toxic levels are essentially
impossible to reach through an overdose of a single antidepressant drug.
Parkinson's disease (1)
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Parkinson's disease is a degenerative disorder of
the central nervous system that often impairs the
sufferer's motor skills and speech.
It is characterized by:
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Change in facial expression (staring, lack of blinking)
Failure to swing one arm when walking
Flexion (stooped) posture
"Frozen" painful shoulder
Limping or dragging of one leg
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.