basal ganglia- student
TRANSCRIPT
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Structure & Function of the Basal
GangliaDr. Claudia Leitner
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Outline
1. Anatomy
2. Physiology
1. Direct Pathway
2. Indirect Pathway
3. Clinical Significance
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1.) ANATOMY
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Basal Nuclei
Masses of gray matter found deep within the
cortical white matter
The corpus striatum is composed of three
parts
Caudate nucleus
Putamen
Globus pallidus Lentiform nucleus
Striatum
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Functional association
With:
Subthalamic nuclei (diencephalon)
Substancial nigra (midbrain)
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Recall that the anterior horn of the lateral ventricle is concave on its
lateral aspect
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The head of the caudate nucleus fits into this concave recess. The rest
of the caudate forms a long curving tapering rod on the side of the
ventricle and ending in the temporal lobe.
Head of
caudate
Tail of
caudate
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Head of caudate
ventricle
Putamen
The caudate forms the lateral wall of the
lateral ventricle (coronal section)
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The putamen is a bean-shaped nucleus lateral to the caudate. It has
links to the caudate by spokes of grey matter that cross the
internal capsule.
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The accumbens nucleus lies at the anterior inferior junction of the
caudate and putamen;
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caudate
Putamenaccumbens
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caudate
putamen
Globus
pallidus (e)
Globus
pallidus (i)
Medial to the putamen (posterior to the accumbens) is a third nucleus, the Globus
pallidus.
GP has two parts, an internal (i) and external (e) part
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The caudate and putamen= (dorsal) striatum.
Striatum means striped and the two regions of grey matter with a white matter sandwich
between them always has a striped appearance.
Dorsal
striatum
The nucleus
accumbens is
referred to as the
ventral striatum
(not visible on this
section)
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The striate arteries leave
the MCA at nearly 90
degrees and are very
prone to rupture and
blockage by an embolus.
The striatum and
internal capsule are
all supplied by the
first part (m1) of the
middle cerebral
artery (MCA). Small
arteries branch off
the MCA and supply
the basal ganglia;
these are the striate
arteries (sometimes
called lateral striate
and medial striate
arteries)
The striate arteries also
supply part of the thalamus
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Substantia nigra
In Midbrain
Source of Dopaminergic
neurons
Axons to straitum
substantia
nigra
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Anatomy Summary
Dorsal Striatum (or just striatum) means caudate & putamen
Ventral Striatum is accumbens
Basal Ganglia normally includes caudate, putamen, both parts of
globus pallidus, substatia nigra and subthalamic nucleus.
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2.) PHYSIOLOGY
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Functions of Basal Nuclei
The following are thought to be functions of
basal nuclei
Regulate intensity of slow or stereotyped
movements
Inhibit antagonistic and unnecessary movement
Influence muscular activity
Regulate attention and cognition
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Striatum
Cortex
Substantial nigra Globus pallidus (internal)
Thalamus
At rest:
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Tonic inhibition of thalamus from GPi, thus no excitation of cortex, thus no movement
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2.1.) DIRECT PATHWAY
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The cortical input to the caudate
and putamen is via excitatory
glutamate neurones.
Both the caudate/putamen and
the globus pallidus contain
mainly GABA-ergic inhibitory
neurones.
When there are two inhibitory
neurones in sequence, there is
inhibition of inhibition, ie overall
excitation. This excitation by
double inhibition is called
DISINHIBITION.
Caudate&
putamen
Globuspallidus
Motor thalamus
CortexDisinhibition in Basal Ganglia:
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Direct Pathway
Striatum
Cortex:Sensory & Association
Cortex
Substantial nigra Globus pallidus (internal)
Thalamus
During movement/changes:
-
+
+
+
DA
Thalamus is no longer inhibited, thus excitation of cortex, thus movement.
The DIRECT pathway is excitatory to the motor thalamus by disinhibition.
Cortex:Primary MC & SMA
X
Glutamate
GABA
Disinhibition
-
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2.2.) INDIRECT PATHWAY
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Striatum
Cortex
Globus pallidus (internal)
Thalamus
At rest:
-
Tonic inhibition of thalamus from GPi, thus no excitation of cortex, thus no movement
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Indirect Pathway
Striatum
Cortex:Sensory & Association
Cortex
Subthalamic nuclei
Globus pallidus (internal)
Thalamus
At Rest:
-
+
Cortex:Primary MC & SMA
Globus pallidus (External) +
-
X
Glutamate
GABA
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AT REST
When you are at rest or doing a repetitive movement (eg walking,
talking) the direct pathway is inactive.
The indirect pathway is active and the subthalamic nucleus and the
internal part of the globus pallidus (GPi) are tonically active. Theyprovide a tonic inhibitory input to the motor thalamus (VL). This
prevents CHANGE in movement : i.e you go on doing what you are
already doing. If you are sitting, you go on sitting, if you are walking.
You go on walking etc.
When you want to CHANGE your ongoing motor program (eg stop
walking, sit down) ie start or stop a particular movement, the direct
pathway become active, an the indirect pathway inactive.
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AT REST
At rest: the indirect pathway is active.
Result: motor thalamus remains fixed, and motor cortex output fixed.
Result: changes in motor programs disallowed
The INDIRECT pathway is INHIBITORY.
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Indirect PathwayDuring Movement/Change:
Striatum
Cortex:Sensory & Association
Cortex
Subthalamic nuclei
Globus pallidus (internal)
Thalamus
+
Cortex:Primary MC & SMA
Globus pallidus (External)
+
-X
Glutamate
GABA
Dopamine
-
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What do the basal ganglia actually do???
Current theories of the basal ganglia is that they have the executive
role in deciding on:
the initiation and sequencing of
voluntary movements.
Enable motor program switching
ANYTHING you do, whether it is quiet sitting, walking, running, can be
considered as a motor program. When you change what you are doing
you stop one motor program and start another. The basal ganglia control
the selection, start and stop points of motor programs.
C ti l
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Striatum
D1 neurones
GPi
thalamus
DA
There are two separate groups of
striatal GABA neurones, one group
expresses the D1 receptor, the
other expresses the D2 receptor.
D1 receptor:
increases cAMP
increases sensitivity of striatal cell
to glutamate
project to Gpi directly (direct
pathway)
Cortical
glutamatergic input
Increasedinhibition
activates
Decreased
inhibition
Dopamine INCREASES action
of direct pathway (D1
receptors).
Dopamine DECREASES action
of indirect pathway (D2
receptors).
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Physiology Summary
Direct pathway: activates motor program change: D1 receptors: activated by
dopamine
Indirect pathway: blocks motor program change: D2 receptors: depressed by
dopamine
Thus overall:
Dopamine, by facilitating the direct pathway and depressing the indirect
pathway, allows motor programs to change and stop and start at will.
Without dopamine, the system would get stuck and the person would be
unable to start or stop movements properly
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Both Pathways
Striatum
Cortex:Sensory & AssociationCortex
Subthal n GP(int)
Thalamus
At Rest:
-
+
Cortex:Primary MC & SMA
GP (ext)
+
-
Subst nigra
No input to Cortex!
Thalamus inhibited.
-X
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Both Pathways
Striatum
Cortex:Sensory & AssociationCortex
Subthal n GP(int)
Thalamus
During Movement/Change:
+
Cortex:Primary MC & SMA
GP (ext)Subst nigra
DA
D1D2
Input to Cortex!
Thalamus not inhibited.
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Both Pathways
Striatum
Cortex:Sensory & AssociationCortex
Subthal n GP(int)
Thalamus
During Movement/Change:
+
Cortex:Primary MC & SMA
GP (ext)
+
-
X
+
Subst nigra
+-
DA
D1D2
Input to Cortex!
Thalamus not inhibited.
X
-
X
- -
X
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3.) CLINICAL SIGNIFICANCE
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Parkinsons Disease (PD)
PD is specifically due to loss of dopaminergic input to caudate andputamen. The cells in the substantia nigra die off. More than 80% of
Substantia Nigra Dopamine cells have to be dead before clinical signs of
PD show themselves.
Loss of black
pigmentation
in Sub. Nig.
indicates loss
of dopamine
containingneurones
Normal brain
with black
pigmentation
https://www.youtube.com/watch?v=ECkPVTZlfP8https://www.youtube.com/watch?v=ECkPVTZlfP8https://www.youtube.com/watch?v=ECkPVTZlfP8https://www.youtube.com/watch?v=ECkPVTZlfP8 -
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Bradykinesia
Rigidity
Resting tremor Gait disturbances: shuffling,
freezing, etc
Postural reflexes impaired;
tendency to fall
Monotonic speech, mask like face
Micrographia
Major Signs of Parkinsons Disease (PD)
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Causes of PD
specifically due to loss of dopaminergic input to caudate and putamen
dopamine cells in substantia nigra have died:
The accumulation of protein is almost certainly secondary to some
other pathological process, such as free radical mediated damage
Excessive iron deposits are often found in the striatum from PD
brains at post mortem (free iron catalyses free radical reactions)
special calcium channels, occuring only on the dopamine neurones,
are damaged and this allows excess calcium entry and subsequent
damage and death.
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Treatment of PD
ALL TREATMENT AT PRESENT PALLIATIVE; NOTHING STOPS RELENTLESS PROGRESS
OF DOPAMINE CELL DEATH
Ideally if one could stop progress of disease at early stage (
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Huntingtons Disease
Hyperkinesis (restlessness, cant keep still)
Extra involuntary movements (Ballismus, Athetosis, Tourette)
Dementia
Due to loss of GABA-ergic neurones in striatum (this can be seen in
MRI as enlargement of ventricles and shrinkage of basal ganglia).
Hereditary- autosomal dominant mutation of Huntingtin gene
Ballismus: involuntary sudden jerky movements
Athetosis: involuntary smooth sinuous movements.
Both caused by damage to cells in striatum.
Management: no cure, neuroleptics (dopamine antagonists) or atypical
antipsychotics may help psychotic symptoms. SSRI for depression, also
benzodiazepines.
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Functions of Basal Nuclei (revisit)
The following are thought to be functions of
basal nuclei
Regulate intensity of slow or stereotyped
movements
Inhibit antagonistic and unnecessary movement
Influence muscular activity
Regulate attention and cognition Motor program switch