Basal Ganglia- Student

8/10/2019 Basal Ganglia- Student

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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:

-

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

Subthalamic nuclei


Thalamus

At Rest:

-

+


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

Subthalamic nuclei


Thalamus

+


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:

-

+


GP (ext)

+

-

Subst nigra

No input to Cortex!

Thalamus inhibited.

-X


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Both Pathways

Striatum


Subthal n GP(int)

Thalamus

During Movement/Change:

+


GP (ext)Subst nigra

DA

D1D2

Input to Cortex!

Thalamus not inhibited.


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Both Pathways

Striatum


Subthal n GP(int)

Thalamus

During Movement/Change:

+


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

Basal Ganglia- Student

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