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Anatomy

6.5

Feb 14, 2012


Dr. Quijano

Basal Ganglia System


OUTLINE
I. Motor Control
II. Basal Ganglia System
A. Components
B. Nomenclature
III. Connections of Basal Ganglia
IV. Basal Ganglia Feedback Loops
V. Basal Ganglia Diseases
A. Parkinsons Disease
B. Chorea

Figure 1.Motor control system. Alpha motor neurons are the final
common path for motor control. Peripheral sensory input and spinal cord
tract signals that descend from the brainstem and cerebral cortex
influence the motor neurons. The cerebellum and basal ganglia contribute
to motor control by modifying brainstem and cortical activity.

Objectives:
Name the 3 systems involved in the suprasegmental mechanism of
voluntary motor control.
Describe the basal ganglia and its composition
Enumerate the sources of the afferent fibers to the basal ganglia.
State the parts of the basal ganglia where almost all the afferent impulses
terminate and where almost all afferent fibers arise.
Name the efferent tracts from the globuspallidus
Trace the different circuitry within the basal ganglia and name the
neurotransmitters involved.
Describe the common basal ganglia disorders

I.MOTOR CONTROL
Evolution of Movement. Movement is a fundamental and
essential property of animal life.
o In simple, unicellular animals, motion depends on the
contractility of protoplasm and the action of accessory organs:
cilia, flagella, etc
o Rudimentary multicellular animals possess primitive
neuromuscular mechanisms
o In more advanced forms of animal life, reflexive motion is
based on the transmission of impulses from the receptor
through the afferent neuron and ganglion cell to motor
neurons & muscles = which is found in the REFLEX ARC.
Reflex arc is seen in higher form of animals with developed
Spinal Cord. Superimposed on these reflex circuits, the Brain
is concerned with the initiation and control of movement and
the integration of complex motions.
Motor system in humans control complex neuromuscular
network. Commands must be sent to many muscles, and many
joints must be stabilized.

Muscular actvity by reflexes (eg. knee jerk reflex) is controlled at


the spinal level.
Stereotypic repetitious movement (eg. walking) is controlled by
spinal cord, brainstem and cerebellum
Specific, goal directed movement (fine motor movement like
buttoning your shirt) is initiated by cerebral cortex.

There are 3 Systems in Suprasegmental Control
1. Pyramidal System
o Direct control over the motor neurons
2. Basal ganglia inhibitory output
o Indirect control over motor neurons (influences motor cortex,
which in turn, brings down the effect to the motor neuron
3. Cerebellum excitatory output
o Also indirect control
Basal Ganglia & Cerebellum modify movement on a minute-to-
minute basis.
Cortical Modulation is thru recurrent circuits.

There are 2 Circuits of Motor System
o Pyramidal System the primary control of voluntary
movement thru (1) corticospinal or the pyramidal tract and (2)
corticotubular pathways
o Extrapyramidal System (EPS) (1) Basal Ganglia is clinically the
EPS and (2) Cerebellum

Figure 2. Motor control and its modulation



Group 2 | Agulto, Agustin B, Al-qaseer, Alano, Alastra, Alegre, Almario

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II. BASAL GANGLIA SYSTEM: Overview


Basal Ganglia are a collection of subcortical nuclei of
telencephalon, subthalamus & midbrain that modulate motor and
cognitive functions of motor complex. (Gilman & Newman)
The term is applied to a collection of masses of gray matter
situated within each cerebral hemisphere which includes the (1)
corpus striatum, (2) amygdaloid nucleus, and (3) the claustrum.
th
(Snell, 7 ed)
Movements influenced by the basal ganglia include those related
to:
o Posture
o Automatic movements (eg. swinging of arms while walking)
o Skilled volitional movements of the trunk and limbs
o It also participates in cognition.

A. Components of the Basal Ganglia
Telencephalic Nuclei
o Caudate (Tail)
o Putamen (shell)
o Globus pallidus (pale)
o Nucleus accumbens (leaning)
HISTORICALY, the claustrum and amygdale

Nontelencephalic Nuclei
o Subthalamic nucleus
o Substantianigra

Figure 3. The components of the basal ganglia.


B. Nomenclature of the Basal Ganglia

Figure 4. Organization of basal ganglia

The term STRIATUM is used to describe the Caudate Nucleus


PLUS the Putamen.
Corpus Striatum is striatum PLUS Lentiform Nucleus.
o striped body
o lateral to the thalamus and divided by sheets of myelinated
fibers and internal capsule into:
Caudate nucleus (tail) C-shaped mass of gray matter. This is
the largest nucleus.
o It lies dorsolateral to the thalamus and is closely related to
the parts of the lateral ventricles.
o It has a head, body and tail
Head
o largest part and continuous and bulges at the cephalic
end
o continuous inferiorly with the putamen of the
lentiform nucleus
o caudate nucleus + putamen = neostriatum or striatum
o forms the lateral wall of the anterior horn of the
lateral ventricle
Body
o Continuous with the head in the region of the
interventricular foramen
o forms part of the floor of the body of the lateral
ventricle
Tail
o Continuous with the body in the region of the
posterior end of the thalamus
o Terminates anteriorly in the amygdaloid nucleus
o Follows the contour of the lateral ventricle and
continues forward in the roof of the inferior horn of
the lateral ventricle
Internal capsule is a small but crucial band of projection fibers
that separate the lentiform nucleus from the medial caudate
nucleus and the thalamus.
o Recall 3 types of fibers: (1) commissural fibers, (2) association
fibers, and (3) projection fibers
Commisural fibers
o Connect corresponding regions of the two hemispheres
(corpus callosum, posterior commisure, fornix, and
habenular commissure)
Association fibers
o Connect various cortical regions within the same
hemisphere and maybe divided into short and long groups
o Short association fibers lie immediately beneath the
cortex and connect adjacent gyri; run transversely to the
long axis of the sulci
o Long association fibers collected into named bundles that
can be dissected in a formalin-hardened brain
Projection fibers
o Afferent and efferent nerve fibers passing to and from the
brainstem to the entire cerebral cortex must travel between
large nuclear masses of gray matter within the cerebral
hemisphere
o At the upper part of the brainstem, these fibers form a
compact band known as the internal capsule
o Afferent & efferent nerve fibers passing to and from the
brainstem to the entire cerebral cortex must travel between
large nuclear masses of gray matter within the cerebral
hemisphere. At the upper part of the brainstem, these fibers
form a compact band the Internal Capsule.
o It is flanked medially by the caudate nucleus and the thalamus.
o Because of the wedge-shaped lenticular nucleus, the internal
capsule is bent to form the anterior limb and a posterior limb
on horizontal section.

Group 2 | Agustin B, Al-Qaseer, Alegre, Almario, Almazan, Almodiente, Altabano, Alvarez

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Lentiform Nucleus
o Thumb-sized mass of gray matter wedged against the internal
capsule
o Wedge-shaped mass of gray matter whose broad convex base is
directed laterally and its blade medially
o Buried deep in the white matter of the cerebral hemisphere and
o Related medially to the internal capsule which separates it from
the caudate nucleus and the thalamus
o Related laterally to a thin sheet of white matter, the external
capsule which separates it from a thin sheet of gray matter called
the the claustrum
o Divided into putamen and globus pallidus
Putamen
Larger and darker lateral portion
Has the same histological appearance as the caudate
nucleus, with numerous and densely packed small neurons
Contains granules with Ach that account for its darker color
Globus Pallidus
Lighter medial region
Contains sparsely distributed large cells and traversed by
many myelinated fibers
Paleness due to the high concentrations of myelinated
fibers
A cell sparse lamina separates the globus pallidus itself
into: external globus pallidus and internal globus pallidus
NOTES:
Almost all efferents from GB arise from GPi (w/c contain the inhibitory
neurotransmitter, GABA
GPi sends (1) Major inhibitory output from BG back to thalamus and (2)
few projections to area of midbrain to assist in postural control
Both GPe and GPi receive info from caudate and putamen
They both are in communication with subthalamic nucleus
They also provide output to substantia nigra
Posterior limb of internal capsule: separates lentiform nucleus from
thalamus
anterior limb of the internal capsule: separates lentiform from head of
caudate nucleus.


Striatum (aka Neostriatum, Dorsal Striatum) = Putamen + Caudate
o Acetylcholine is the neurotransmitter of interneurons
o An acetylcholinesterase (AChE) stains for the enzyme that
degrades acetylcholine (ACh).
o It receives major inputs to the basal ganglia provided by
afferents from the cerebral cortex, thalamus and substantia
nigra.
o Receives excitatory input from neurons in all areas of the
isocortex, causing excitation w ith GABA as the neurotrans
mitter
o Stimulation of cerebral cortical neurons evoke sequences of
excitatory(fromglutamatergiccorticalefferents),followedby
inhibitory postsynaptic potentials (from GABA-ergic
interneurons in striatum)
o Projections have a topographic organization that is continued
by neurons that project from the substantia nigra pars
reticulate and to the internal and external globus pallidus
o Neurons from the striatum to the external pallidum provide
inhibition using GABA and encephalin
o Neurons from striatum to the internal pallidum also inhibit
using GABA and Substance P

Projection
Areas
Putamen
Areas 4, 6 (lateral and medial) and 3,1,2
Caudate nucleus
Frontal eye fields and association areas of the
frontal and parietal lobes


Amygdaloid Nucleus
o Situated in the temporal close to the uncus
o Considered part of the limbic system
o Influences the bodys response to environmental changes

Claustrum
o Thin sheet of gray matter that is separated from the lateral
surface of the lentiform nucleus by the external capsule
o Lateral to the claustrum is the subcortical white matter of the
insula
o Function is still unknown

Figure 5. Striatum (putamen and capsule)


NON-TELENCEPHALIC NUCLEUS:
Subthalamic Nuclei
o part of diencephalon
o largest nuclear mass in the subthalamus
o Shape of a biconvex lens between thalamus & tegmentum, just
rostral to midbrain
o Has important connections with corpus striatum; as a result
needed for the integration of smooth movements of different
parts of the body
o Disorders: Ballism/Hemiballism
o Main mass of midbrain between cerebral peduncles and
cerebral aqueducts
o Functionally closely related to the activities of the basal nuclei
o Neurons are glutaminergic and excitatory
o Have many connections to the globus pallidus and substantia
nigra
Substantia Nigra
o Non-telencephalic nucleus = lies in upper midbrain; between
the cerebral peduncle & tegmentum
o The nucleus is composed of medium-size multipolar neurons
that possess inclusion granules of melanin pigment within their
cytoplasm
o In a brain specimen, SN neurons appear brownish-black due to
neuromelanin
o The SN neurons are dopaminergic and inhibitory ( + ; - )
o It is concerned with muscle tone and is connected to the cerebral
cortex, spinal cord, hypothalamus, and basal nuclei
o Neuromelanin gives its color: black substance
o Have many connections to the corpus striatum
o It has 2 superior and 2 inferior colliculi
o 2 parts of the Substantia Nigra

Group 2 | Agustin B, Al-Qaseer, Alegre, Almario, Almazan, Almodiente, Altabano, Alvarez

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Substancia Nigra pars compacta (SNc) this is the part that


degenerates in Parkinsons disease. It is treated by giving oral
dopamine precursors.
o Receives input from striatum and sends it back to striatum
or sends it to the outside of the basal ganglia to control
head and eye movement
SubstanciaNIgra pars reticulata (SNr) porjects to superior
colliculi and uses GABA as a neurotransmitter

III. CONNECTIONS OF BASAL GANGLIA
Generalization (REMEMBER!)
ALMOST ALL of the input or afferent fibers are received by the
STRIATUM. The GLOBUS PALLIDUS (mainly the interna, or medial
part) forms the major site from which the output or efferent fibers
leave the basal nuclei.

Afferent fibers TO the striatum or basal ganglia:
1. Cerebral cortex the corticostriate fibers
Preferentially: From the cerebral cortex to the putamen
Only some fibers (from Area 8) will go to caudate nucleus
Primary Motor cortex (MI) = Area 4
Supplementary Motor Cortex (MII) = Area 6
Pre Motor Area = Area 6
Somotosensory cortices = Area 3,1,2
Uses Glutamate as its neurotransmitter (strongly excitatory)

Figure 7. Some of the major connections between the cerebral cortex, the
basal nuclei, the thalamic nuclei, the brainstem, and the spinal cord.



Figure 8. Basal nuclei pathways showing the known neurotransmitters.

Figure 6. Schematic diagram of prinicipal connections of basal ganglia.


2. Thalamus (only from intralaminar nuclei/centromedian)


thalamostriate fibers
3. Substantia nigra nigrostriate fibers using dopamine as its
neurotransmitter. Overall effect is inhibitory. Involved in
Parkinsons disease.
4. Brainstem striatal fibers using serotonin. Inhibitory.

Efferent fibers FROM the Striatum:


1. Striatopallidal fibers
GPE = strong inhibitory input
GPI
2. Stiratonigral fibers inhibitory

Efferent fibers FROM the Globus Pallidus = Pallidofugal fibers
1. Fasciculus Lenticularis to subthalamus (across posterior limb
of internal capsule)
2. Ansa Lenticularis to thalamic nuclei (loop around the ventral
aspect of posterior limb of internal capsule; ansa=loop)
3. Pallidosubthalamic fibers to subthalamic nucleus (STN)
4. Pallidotegmental fibers to caudal tegmentum (from ansa
lenticularis, it could go down to tegmentum and form the
pallidotegmental fibers)
Fasciculus lenticularis + Ansalenticularis = Thalamic fasciculus


ALMOST all impulses terminate in the Striatum are excitatory
Interneurons within the striatum are excitatory and use Ach.

Group 2 | Agustin B, Al-Qaseer, Alegre, Almario, Almazan, Almodiente, Altabano, Alvarez

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(e.g. striatum inhibits GPI/SNr which is an inhibitor of thalamus, so


thalamus will be released from the inhibiting effect of GPI/SNr)

Basal Ganglia efferent fibers TO the brainstem:


o Superior colliculus regulation of saccadic eye movements
o Pedunculopontinetegemental neuron (PPTN) coordinates
status of arousal with fundamental motor patterns (REM)

Figure 9. Principal physiologic circuitry and neurotransmitters in the basal


ganglia.


IV. BASAL GANGLIA FEEDBACK LOOPS
1. Cortico + striato pallido thalamo + cortical pathway
o It is the long loop
o From cortex to striatum, and thalamus to cortex, it is excitatory
o From striatum to globus pallidus, and pallidus to thalamus, it is
inhibitory
2. Direct loop (nigrostriatal fibers)
o Cortico + striato pallido/snr thalamo + cortical pathway
o D1 receptors on striatum are stimulated, which are excitatory
o Cortex striatum SNr-SNc striatum(D1) G pallidus
thalamus back to cortex

Figure 10. Direct and indirect Loop


Black arrows represents excitatory effect, red arrows represents inhibitory
effect.
REMEMBER:
excitatory stimulus to an inhibitor, will increase its ability to inhibit (e.g.
cortex to striatum)
inhibitory stimulus to an inhibitor, will decrease its ability to inhibit, thus
releasing/exicitng/stimulating the succeeding nuclei

3. Indirect loop (nigrostriatal fibers) the subthalamic nucleus


influence the outflow of the globus pallidus interna.
o Cortico + striato pallido ext stn + pallido int/snr thalamo
cortical pathway
o D2 receptors are stimulated, which are inhibitory
o Cortex striatum SNr-SNc striatum(D2) G
pallidus(ext.) subthalamic nucleus G pallidus (int.)
thalamus cortex
o The striatal efferent fibers reach the external segment of the
GP and after synspases, pallidal efferent fibers cross the
posterior limb of the internal capsule to reach the subthalamic
nucleus (STN).
o Neurons of the STN project excitatory glutamatergic fibers back
to both GP, but primarily to the internal segment, and to the
substantia nigra reticulate (SNr) where they excite GABAergic
projections to the thalamus and thereby inhibit it.
o The STN also receive direct input from the cerebral cortex.
Memory trick for Neurotransmitters:
All excitatory stimulus uses glutamate
All inhibitory stimulus uses GABA
EXCEPT for Dopamine from SNCompacta
o Dopamine in INdirect loop (D2) is Inhibitory (IN-IN)
o Dopamine in direct loop (D1) is excitatory
OVERALL basal ganglia effect: INHIBITORY
The Basal ganglia function is described as the brake hypothesis.
Ex: To sit still, put the brakes on and all movements except those
reflexes that maintain an upright posture. To move, apply a brake to
some postural reflexes and release brake on voluntary movement.
The disturbances could lead to:
1. Presence of extraneous unwanted movements
2. Absence or difficulty with intended movements

V. BASAL GANGLIA DISEASES
The are three functional categories (Manter&Gatz):
o Parkinsonism degeneration of the substantia nigra
o Hyperkinetic movement (Ballism, chorea, athetosis) from
striatal or subthalamic dysfunction
o Dystonia from pallidal dysfunction

Two General Types (Snell):
o Hypokinetic disorders lack or slowness of movement
o Hyperkinetic movemnt excessive and abnormal movements
(ballism, chorea, athetosis)
Parkinsons disease includes both types

A. Parkinsons Disease
Results from slow and steady loss of dopaminergic neurons in
SNc.
Aka Paralysis Agitans
Concerned with lesions on the basal ganglia
Symptoms usually include the ff:
o Tremors when at rest (pin-rolling movement)
o Rigidity due to simultaneous contraction of flexors and
extensors (cogwheel rigidity)
o Bradykinesia or slow movement
st
o Festinating gait difficulty initiating 1 steps, but once under
way, pace becomes more rapid (short, shuffling steps) and has
trouble stopping

Group 2 | Agustin B, Al-Qaseer, Alegre, Almario, Almazan, Almodiente, Altabano, Alvarez

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o Postural disturbances stooped posture with loss of arm swing


when walking
o Masked face expressionless
o Depression and anxiety problems with memory loss and
dementia
o No loss of muscle power nor sensiblities
Parkinsons usually develop late in life.
REMEMBER: Parkinsons disease involves the nigrostriatal
dopaminergic pathway

Figure 11. Section of the brain affected by Parkinsons disease

Basal ganglia affects final common path or LMN INDIRECTLY


Basal ganglia effects are contralateral to the side of the lesion
Strength persists in muscles but there is emergence of involuntary
movement.


B. Chorea
A form of striatal disorder
Exhibits involuntary, quick, jerky, irregular nonrepetitive
movements. Ex: swift grimaces and sudden movements of limbs
and head.
May affect limbs (refers more to distal movements), face, tongue

Huntingtons disease hereditary, defect on chromosome 4
(protein huntingtin).
o Degeneration of neurons of caudate nucleus
o Disease is characterized by chorea and progressive dementia

Sydenhams Chorea aka St. Vitus Dance
o Disease of childhood
o Associated with rheumatic fever (streptococcal antigens have
same membrane proteins of striatal neurons)
o Choreic movements
o Disease is transient and with full recovery

Athetosis
o Characterized by slow writhing worm-like involuntary
movement of extremities, trunk, and neck
o Involves the cerebral cortex and the basal ganglia
o Ex: TICS, Tourettessyndrom
o Aka choreoathetosis

Dystonia
o Fixed posture or sustained postural contraction of limb, neck
and facial muscles
o Most commonly secondary to cerebral palsy

Ballism or Hemiballismus
o Involuntary flailing movements of arm/s and leg/s
o Caused by damage (i.e. stroke) of opposite subthalamic
nucleus.

Group 2 | Agustin B, Al-Qaseer, Alegre, Almario, Almazan, Almodiente, Altabano, Alvarez

Figure 12. A. Conceptual model of activity in the basal ganglia and


associated and associated thalamocortical regions under normal
circumstances. Dark arrows indicate inhibitory connections, and open
arrows indicate excitatory connections. B. Changes in activity in
Parkinsons disease. As a result of degeneration of the pars compacta of
the substantia nigra, differential changes occur in the two striatopallidal
projections (as indicated by altered thickness of the arrows), including
increased output from GPi to the thalamus. D, direct pathway; I, indirect
pathway; GPe, external segment of globus pallidus; GPi, internal segment
of globus pallidus; SNr, substantia nigra (pars reticulate); SNc, subsantia
nigra (pars compacta); STN, subthalamic nucleus; VL, ventrolateral
thalamus.

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