BASAL GANGLIA

Dr. Chandana Hewage

Senior lecturer
FMS-USJP
22. 7. 2018
 Objective
• Describe the functions of basal ganglia
• Explain the physiological basis of dysfunctions
of basal ganglia in relation to the Parkinson’s d
isease
Basal ganglia (BG)
 Introduction-BASAL GANGLIA
• The term basal nuclei is applied to a collection of m
asses of gray matter situated within each cerebral h
emisphere (subcortical nuclear masses).
• Clinicians and neuroscientists use a variety of differ
ent terminologies to describe the basal nuclei.
• The interconnections of the basal nuclei are comple
x.
• The basal nuclei play an important role in the contr
ol of posture and voluntary movement.
 Introduction cont’
• They are
–caudate nucleus
–Putamen
–globus pallidus
–subthalamic nucleus
–substantia nigra.
• The caudate nucleus and putamen collectively for
m the striatum; the putamen and globus pallidus c
ollectively form the lenticular nucleus
 Globus pallidus

external segments Internal segments (Gp

e) (GPi)
• Both regions contain inhibitory GABAergic ne
urons.
Substantia nigra

pars compacta pars reticulata

(dopaminergic) (GABAergic )
 Introduction cont’
• There are at least four neuronal types within the st
riatum.
• About 95% of striatal neurons are medium spiny n
eurons that use GABA as a neurotransmitter.
• The remaining striatal neurons are all aspiny intern
eurons that differ in terms of size and neurotrans
mitters: large (acetylcholine), medium (somatostat
in), and small (GABA).
 The major afferent pathways in the B
G
• Two main inputs to the BG are from
• cerebral cortex ( corticostriate pathway )
• intralaminar nuclei of the thalamus ( thalamostriatal pa
thway ).

• Both are excitatory and the neurotransmitter is glu

tamate , and they both terminate in the striatum.
 The major efferent pathways in the B
G
• Major outputs of the basal ganglia are from GPi an
d substantianigra pars reticulata.
• Both are inhibitory (GABAergic) and both project to
the thalamus and braintem.
• From the thalamus, there is an excitatory (presuma
bly glutamate) projection to the prefrontal and pre
motor cortex.
• This completes a full corticalbasal ganglia-thalamic
-cortical loop.
GPe, external segment
of the globus pallidus
GPi, internal segment of the gl
obus pallidus
PPN, pedunculopontine nuclei
SNC, pars compacta of the su
bstantia Nigra
STN, subthalamic nucleus
Thal, thalamus.

BG out put to the motor syste

m is inhibitory
 The connections within the BG
• Dopaminergic nigrostriatal projection from the
substantia nigra pars compacta to the striatum
• There is an inhibitory projection from the striatu
m to both GPe and GPi.
• The subthalamic nucleus receives an inhibitory i
nput from Gpe
• Subthalamic nucleus has an excitatory (glutama
te) projection to both GPe and GPi
 Basal Ganglia-functions

• The basal ganglia, like the cerebellum, constit

ute another accessory motor system that func
tions in close association with the cerebral cor
tex and corticospinal motor control system.
• The basal ganglia receive most of their input si
gnals from the cerebral cortex itself and also r
eturn all their output signals back to the corte
x and brainstem
Basal Ganglia-functions
 Functions of BG

• Neurons in the basal ganglia like those in

the lateral portions of the cerebellar hem
ispheres, discharge before the onset of
movements
• So the basal ganglia are involved in the pl
anning and programming of movement (
I.e an abstract thought is converted into
voluntary action)
 Functions of the Basal Nuclei
• The basal nuclei not only influence the execution o
f a particular movement but also help prepare for
the movements (planning).
• The activity in certain neurons of the globus pallid
us increases before active movements take place i
n the distal limb muscles.
• This important preparatory function enables the tr
unk and limbs to be placed in appropriate position
s before the primary motor part of the cerebral co
rtex activates discrete movements in the hands an
d feet.
 Basal Ganglia-functions cont’
• One of the principal roles of the basal ganglia in
motor control is to function in association with th
e corticospinal system to control complex pattern
s of motor activity.
• An example is the writing of letters of the alphab
et. When there is serious damage to the basal ga
nglia, the cortical system of motor control can no
longer provide these patterns. Instead, one's writi
ng becomes crude, as if one were learning for the
first time how to write.
• Two important capabilities of the brain in contro
lling movement are timing and scale of the move
ment
• to determine how rapidly the movement is to
be performed
• to control how large the movement will be.
I.E can write the letter "a" slowly or rapidly. OR
write a small "a“ or a large "a"
Regardless of the choice, the proportional char
acteristics of the letter remain nearly the sam
e.
 Functions of BG
• BG influence the motor cortex via the thalamus, an
d the corticospinal pathways provide the final com
mon pathway to motor neurons
• Further Gpi projects to nuclei in the brain stem, an
d from there to motor neurons in the brain stem a
nd spinal cord.
• The caudate nuclei, also play a role in some cogniti
ve processes through the interconnections of with
the frontal portions of the neocortex
 Biochemical basis and the disease in
the BG
• Three distinct biochemical pathways in the basal g
anglia normally operate in a balanced fashion:
(1)the nigrostriatal dopaminergic system
(2)the intrastriatal cholinergic system
(3)the GABAergic system, which projects from the st
riatum to the globus pallidus and substantia nigra.
• When these pathways become dysfunctional, char
acteristic motor abnormalities occur.
 Movement disorders in BG abnor
malities
• Diseases of the basal ganglia results two pattern of
motor disorders:
• hyperkinetic and hypokinetic.
• Hyperkinetic conditions are those in which moveme
nt is excessive and abnormal, including chorea, athe
tosis, and ballism.
• Hypokinetic abnormalities include akinesia and bra
dykinesia.
• Parkinson disease (paralysis agitans) is the common
est disease that affect the functions of BG
 Movement disorders in BG abnor
malities cont’
• Chorea is characterized by rapid, involuntary “dancing
” movements.
• Athetosis is characterized by continuous, slow writhin
g movements.
• Choreiform and athetotic movements have been likene
d to the start of voluntary movements occurring
• in an involuntary, disorganized way.
• In ballism, involuntary flailing, intense, and violent mo
vements occur.
• Akinesia is difficulty in initiating movement and decrea
sed spontaneous movement.
• Bradykinesia is slowness of movement
 PARKINSON DISEASE (PD)
• PD has both hypokinetic and hyperkinetic features.
• It was originally described in 1817 by James Parkins
on and is named for him.
• PD is the first disease identified as being due to a d
eficiency in a specific neurotransmitter
• I.E It was shown to result from the degeneration of
dopaminergic neurons in the substantia nigra pars c
ompacta (which project to the putamen (part of t
he striatum) are most severely affected).
• Parkinson's disease (PD) is a chronic
progressive neurodegenerative disease that is
clinically manifested by a triad of cardinal
motor symptoms - rigidity, bradykinesia and
tremor
 Hypokinetic & hyperkinetic featur
es of Parkinson disease
1.Hypokineticc features of Parkinson disease
• Akinesia and bradykinesia
• Absence of motor activity
• Difficulty in initiating voluntary movements are striking.
• There is a decrease in the normal, unconscious movem
ents such as swinging of the arms during walking
• Loss of facial expressions related to the emotional chan
ges
• Absence of “fidgety” actions and gestures
2.Rigidity
• Rigidity is different from spasticity because in that b
oth the agonist and antagonist muscles have hypert
onia
• lead pipe rigidity
• Passive motion of an extremity meets with a plastic, dea
d-feeling resistance that has been likened to bending a le
ad pipe.
• cogwheel rigidity
• `A series of “catches” takes place during passive motion)
• No sudden loss of resistance.
3. Tremor at rest
• The tremor, which is present at rest and disappears
with activity, is due to regular, alternating 8-Hz cont
ractions of antagonistic muscles.
Pathogenesis of in Parkinson disea
se cont’
 Pathogenesis of the movement
disorders in Parkinson disease
• In normal individuals, basal ganglia output is inhibit
ory via GABAergic nerve fibers.
• Dopaminergic neurons that project from the substa
ntia nigra to the putamen normally have two effects
:
• stimulate the D 1 dopamine receptors, which inhibit GPi
via direct GABAergic receptors,
• inhibit D 2 receptors, which also inhibit the GPi.
• In addition, the inhibition reduces the excitatory dis
charge from the subthalamic nucleus to the GPi.
 Pathogenesis of in Parkinson disea
se cont’
• Ultimately the net effect of GB output is decrease i
n inhibitory output to the thalamus and brain stem
 Pathogenesis of in Parkinson disea
se cont’
• In Parkinson disease, the dopaminergic input to the
putamen is lost resulting decreased inhibition and i
ncreased excitation from the subthalamic nucleus t
o the GPi.
• The overall increase in inhibitory output to the tha
lamus and brain stem disorganizes movement.
 Pathogenesis of in Parkinson disea
se cont’
• An important consideration in Parkinson disease is t
he balance between the excitatory discharge of chol
inergic interneurons and the inhibitory dopaminergi
c input in the striatum.
• Some improvement is produced by decreasing the
cholinergic influence with anticholinergic drugs.
 Treatment of PD
• There is no cure for Parkinson disease, and drug the
rapies are designed to treat the symptoms.
• The main treatemnt are
1. Drugs
2. Use of deep brain stimulation (DBS)
3. Surgical treatments
• surgical lesions of GPi (pallidotomy) or in the subt
halamic nucleus ( thalamotomy )
• to implant dopamine-secreting tissue in or near th
e basal ganglia
 Drugs treatment of PD(L-Dopa)
• More dramatic improvement is produced by a
dministration of L-dopa (levodopa).
• Unlike dopamine, this dopamine precursor cr
osses the blood–brain barrier and helps repair
the dopamine deficiency.
• However, the degeneration of these neurons c
ontinues and in 5–7 years the beneficial effect
s of L-dopa disappear