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BASAL GANGLIA
Dr SHANAVAS C
DEPT OF NEUROSURGERY,
GOVT MEDICAL COLLEGE,
KOZHIKODE
• Basal ganglia - “Basal nuclei”
• Collection of masses of gray matter
(subcortical nuclei) situated at the base of
forebrain and top of midbrain within each
cerebral hemisphere
• control of posture and voluntary
movement (Contralateral side)
Basal Nuclei
• Traditionally includes lentiform nucleus,
caudate nucleus, claustrum, amygdaloid
nucleus.
• Functionally includes lentiform nucleus,
caudate nucleus, ventral striatum (nucleus
accumbens +olfactory tubercle) subthalamic
nucleus and substantia nigra.
Basal Ganglia
1. Neostriatum
Caudate nucleus
Putamen
Ventral striatum (nucleus accumbens)
2. Paleostriatum
Globus pallidus external segment (GPe)
Globus pallidus internal segment (GPi)
3. Substantia Nigra
Pars compacta (SNc)
Pars reticulata (SNr)
4. Subthalamic nucleus (STN)
• Lentiform nucleus - Globus pallidus plus
putamen
• Corpus striatum - Caudate nucleus plus
lentiform nucleus
• Neostriatum (striatum) - Caudate nucleus plus
putamen and ventral striatum (i.e.The nucleus
accumbens, along with the nearby olfactory
tubercle)
• Amygdaloid body - Amygdaloid nucleus
• The pallidum (paleostriatum) (globus pallidus ) –
a part of the lentiform, which is comprised of a
lateral segment ( Gpe) and a medial segment
(Gpi).
• The medial segment has a midbrain extension
known as the reticular part (pars reticulata) of the
substantia nigra. The pigmented, compact part
(pars compacta) of substantia nigra.
From Neuroscience,
Purves et al. eds., 2001
Forebrain
Midbrain
• Corpus Striatum
• Situated lateral to the thalamus and is almost
completely divided by a band of nerve fibers, the
internal capsule, into the caudate nucleus and the
lentiform nucleus.
• “ striatum “ - derived from the striated appearance
produced by the strands of gray matter passing
through the internal capsule and connecting the
caudate nucleus to the putamen of the lentiform
nucleus
Caudate Nucleus
• The caudate nucleus is a large C-shaped mass of
gray matter that is closely related to the lateral
ventricle and lies lateral to the thalamus.
• The lateral surface of the nucleus is related to
the internal capsule, which separates it from the
lentiform nucleus.
• It can be divided into a head, a body, and a tail.
• The head of the caudate nucleus is large and
rounded and forms the lateral wall of the
anterior horn of the lateral ventricle.
• The head is continuous inferiorly with the
putamen of the lentiform nucleus
• The body of the caudate nucleus is long and
narrow and is continuous with the head in the
region of the interventricular foramen.
• The body of the caudate nucleus forms part of
the floor of the body of the lateral ventricle
• The tail of the caudate nucleus is long and
slender and is continuous with the body in the
region of the posterior end of the thalamus.
• It follows the contour of the lateral ventricle
and continues forward in the roof of the
inferior horn of the lateral ventricle.
• It terminates anteriorly in the amygdaloid
nucleus
• Lentiform Nucleus
• The lentiform nucleus is a wedge-shaped mass of
gray matter whose broad convex base is directed
laterally and whose blade is directed medially.
• It is buried deep in the white matter of the
cerebral hemisphere and is related medially to
the internal capsule, which separates it from the
caudate nucleus and the thalamus.
• The lentiform nucleus is related laterally to a
thin sheet of white matter, the external
capsule, which separates it from a thin sheet
of gray matter, called the claustrum.
• The claustrum,in turn, separates the external
capsule from the subcortical white matter of
the insula.
• A vertical plate of white matter divides the
nucleus into a larger, darker lateral portion, the
putamen, and an inner lighter portion, the globus
pallidus
• The paleness of the globus pallidus is due to the
presence of a high concentration of myelinated
nerve fibers.
• Inferiorly at its anterior end, the putamen is
continuous with the head of the caudate nucleus.
• Amygdaloid Nucleus
• The amygdaloid nucleus is situated in the temporal
lobe close to the uncus. The amygdaloid nucleus is
considered to be part of the limbic system.
• Through its connections, it can influence the body's
response to environmental changes. In the sense
of fear, for example, it can change the heart rate,
blood pressure, skin color, and rate of respiration.
• Substantia Nigra and Subthalamic Nuclei
• The substantia nigra of the midbrain and the
subthalamic nuclei of the diencephalon are
functionally closely related to the activities of the
basal nuclei.
• The neurons of the substantia nigra are
dopaminergic and can be excitatory or inhibitory
and have many connections to the corpus striatum
• The neurons of the subthalamic nuclei are
glutaminergic and excitatory and have many
connections to the globus pallidus and
substantia nigra
• Claustrum
• The claustrum is a thin sheet of gray matter that
is separated from the lateral surface of the
lentiform nucleus by the external capsule . Lateral
to the claustrum is the subcortical white matter
of the insula. The function of the claustrum is
unknown
EMBRYOLOGY
• Connections of the Corpus Striatum and
Globus Pallidus
• The caudate nucleus and the putamen form
the main sites for receiving input to the basal
nuclei.
• The globus pallidus forms the major site from
which the output leaves the basal nuclei.
• They receive no direct input from or output to
the spinal cord.
• Connections of the Corpus Striatum
• Afferent Fibers
1) Corticostriate Fibers
• All parts of the cerebral cortex send axons to the
caudate nucleus and the putamen.
• Each part of the cerebral cortex projects to a
specific part of the caudate-putamen complex.
• Most of the projections are from the cortex of the
same side.
• The largest input is from the sensory-motor
cortex. Glutamate (excitatory) is the
neurotransmitter of the corticostriate fibers.
Thalamostriate Fibers
• The intralaminar nuclei of the thalamus send
large numbers of axons to the caudate nucleus
and the putamen
• Nigrostriate Fibers
• Neurons in the substantia nigra send axons to
the caudate nucleus and the putamen and
liberate dopamine at their terminals as the
neurotransmitter.
• It is believed that these fibers are inhibitory in
function.
• Brainstem Striatal Fibers
• Ascending fibers from the brainstem end in
the caudate nucleus and putamen and liberate
serotonin at their terminals as the
neurotransmitter.
• It is thought that these fibers are inhibitory in
function
• Efferent Fibers
• Striatopallidal Fibers
• Striatopallidal fibers pass from the caudate
nucleus and putamen to the globus pallidus
(Gpe) and (Gpi).
• They have gamma-aminobutyric acid (GABA)
(inhibitory) as their neurotransmitter.
• Striatonigral Fibers
• Striatonigral fibers pass from the caudate nucleus
and putamen to the substantia nigra.
• Some of the fibers use GABA or acetylcholine as
the neurotransmitter, while others use substance
P.
• Connections of the Globus Pallidus
• Afferent Fibers
• Striatopallidal Fibers
• As explained above
• Efferent Fibers
• Pallidofugal Fibers
• Pallidofugal fibers are complicated and can be
divided into groups:
• (1) the ansa lenticularis, which pass to the thalamic
nuclei.
• (2) the fasciculus lenticularis, which pass to
the subthalamus;
• (3) the pallidotegmental fibers, which
terminate in the caudal tegmentum of the
midbrain; and
• (4) the pallidosubthalamic fibers, which pass
to the subthalamic nuclei
VENOUS DRAINAGE
• The deep cerebral veins drain the corpus striatum,
thalamus, and choroid plexuses.
• A thalamostriate vein drains the thalamus and
caudate nucleus. Together with a choroidal vein, it
forms the internal cerebral vein. The two internal
cerebral veins unite beneath the corpus callosum to
form the great cerebral vein (of Galen).
Functional organisation of basal
ganglia and other pathaways
• The basal ganglia has dense internuclear
connections.
• Five parallel and separate closed circuits
through the basal ganglia have been
proposed.
• These are the motor, oculomotor, dorsolateral
prefrontal, lateral orbitofrontal, and limbic
loops (Rodriguez-Oroz et al., 2009 )
• It is now generally agreed that these loops
form three major divisions— sensorimotor,
associative, and limbic—that are related to
motor, cognitive, and emotional functions,
respectively
• Within each basal ganglia circuit lies an
additional level of complexity.
• Each circuit contains two pathways by which
striatal activity is translated into pallidal
output.
• These two pathways are named the direct and
indirect pathways, depending on whether striatal
outflow connects directly with the GPi or first
traverses the GPe and STN before terminating in
the GPi.
• The direct and indirect pathways have opposite
effects on outflow neurons of the GPi and SNr.
• In the motor direct pathway, excitatory
neurons from the cerebral cortex synapse on
putamenal neurons, which in turn send
inhibitory projections to the GPi and its
homolog, the SNr.
• The GPi/SNr sends an inhibitory outflow to
the thalamus
• Activity in the direct pathway disinhibits the
thalamus, facilitating the excitatory
thalamocortical pathway and enhancing
activity in its target, the motor cortices.
• Thus, the direct pathway constitutes part of
an excitatory cortical-cortical circuit that likely
functions to maintain ongoing motor activity
• In the indirect pathway, excitatory axons from
the cerebral cortex synapse on putaminal
neurons.
• These neurons send inhibitory projections to
the GPe, and the GPe sends an inhibitory
projection to the STN.
• The net effect of these projections is
disinhibition of the STN. The STN in turn has
an excitatory projection to the Gpi.
• Activity in the indirect pathway thus excites
the GPi/SNr, which in turn inhibits the
thalamocortical pathway.
• Thus, the net effect of increased activity in the
indirect pathway is cortical inhibition.
• DOPAMINERGIC and CHOLINERGIC Modulation
of Direct and Indirect Pathways
• DOPAMINE is produced by cells in the pars
compacta of the substantia nigra (SNc).
• Nigrostriatal axon terminals release dopamine
into the striatum.
• Dopamine has an EXCITATORY effect upon cells in
the striatum that are part of the Direct Pathway,
via D1 receptors.
• Dopamine has an INHIBITORY effect upon
striatal cells associated with the Indirect
Pathway, via D2 receptors
• Both of these effects lead to increased motor
activity
• Cholinergic (Ach) interneurons synapse on the
GABAergic striatal neurons that project to GPi
AND on the striatal neurons that project to GPe.
• The cholinergic actions INHIBIT striatal cells of the
Direct pathway and EXCITE striatal cells of the
Indirect pathway.
• Thus the effects of ACh are OPPOSITE the effects
of dopamine on the direct and indirect pathways
and decrease motor activity.
• Functions of motor loop:
• They seem to be involved in scaling the strength
of muscle contractions and, in collaboration with
SMA, in organizing the requisite sequences of
excitation of cell columns in the motor cortex.
• They come into action after the corticospinal
tract has already been activated by ‘premotor’
areas including the cerebellum.
• it is believed that the putamen provides a
reservoir of learned motor programs which it
is able to assemble in appropriate sequence
for the movements decided upon, and to
transmit the coded information to SMA
• Cognitive loop (prefrontal)
• The head of the caudate nucleus receives a
large projection from the prefrontal cortex,
and it participates in motor learning.
• The VA nucleus completes an ‘open’ cognitive
loop through its projection to the premotor
cortex, and a ‘closed’ loop through a return
projection to the prefrontal cortex.
• The cortical connections of the caudate
suggest that it participates in planning ahead,
particularly with respect to complex motor
intentions.
• Limbic loop:
• This loop passes from inferior prefrontal
cortex through nucleus accumbens (anterior
end of the striatum) and ventral pallidum,
with return via the mediodorsal nucleus of
thalamus to the inferior prefrontal cortex.
• The limbic loop is likely to be involved in giving
motor expression to emotions, e.g. through
smiling or gesturing, or adoption of aggressive or
submissive postures.
• The loop is rich in dopaminergic nerve endings,
and their decline may account for the mask-like
facies and absence of spontaneous gesturing
characteristic of Parkinson’s disease, and for the
dementia which may set in after several years.
• Oculomotor loop:
• The oculomotor loop commences in the
frontal eye field and posterior parietal cortex
(area 7). It passes through the caudate nucleus
and through the reticular part of the
substantia nigra (SNpr).
• It returns via the ventral anterior nucleus of
the thalamus to the frontal eye field and
prefrontal cortex.
• SNpr sends an inhibitory GABAergic projection
to the superior colliculus, where it synapses
upon cells controlling automatic saccades.
• These cells are also supplied directly from the
frontal eye field
• While the eyes are fixated, SNpr is tonically
active. Whenever a deliberate saccade is about to
be made toward another object, the oculomotor
loop is activated and the superior colliculus is
disinhibited.
• In PD oculomotor hypokinesia is due to faulty
disinhibition of the superior colliculus following
associated neuronal degeneration within SNpr.
Disorders of basal ganglia
Hyperkinetic disorders
• excess direct pathway output
• insufficient indirect pathway output
• seen with chorea, athetosis, and ballism
Hypokinetic disorders
• insufficient direct pathway output
• excess indirect pathway output
• Parkinson disease includes both types of motor
disturbances.
• classically described as triad of rigidty,
bradykinesia, tremor
• dopaminergic neurons in substantia nigra pars
compacta are lost in Parkinson’s disease.
• The degenerating nigral dopaminergic cells
accumulate deposits of protein called Lewy Bodies.
• The SN lesion takes away the dopaminergic
drive on the direct pathway at the same time
ACh interneurons are still inhibiting the
striatal cells at the head of the direct pathway
leads to double inhibition of direct pathway
and less active cortex.
• a STN lesion increases activity in the indirect
pathway, which turns DOWN motor activity
• This results in hypokinetic symptoms such as
akinesia (no movement) or bradykinesia (slow
movement)
• In PD, rigidity is present in all muscle groups,
both flexor and extensor, leads to cog wheel
and lead pipe rigidity
• Normally, both corticospinal and reticulospinal
fibers are tonically facilitatory to 1b inhibitory
internuncials.
• In PD, activation of the primary motor cortex
by SMA is known to be both reduced and
oscillatory, thus accounting for the
pronounced effects in the forearm and hand.
• Impaired reticulospinal activity is more likely to
be significant with respect to the lower limbs
• This explains rigidity and static tremors ( 3-6 hz)
in PD.
• Treatment of PD
• Hypokinetic pt are treated with dopamine
agonist like L-dopa or drugs that decrease the
level of Ach in the striatum.
• Parkinson’s disease can be reduced or
alleviated by placing stimulating electrodes in
the thalamus, subthalamic nucleus, or
pallidum
• Thalamic stimulators seem to be effective in
reducing tremor, but do little for akinesia.
• Pallidal stimulation seems to have a more all-
encompassing therapeutic effect
• Pallidotomy also shown some improvement
parkinsonian features
• Two classic hyperkinetic disorders are
hemiballism and Huntington’s chorea
Hemiballism
• characterized by wild, flinging movements of the body
• results from lesion in the subthalamic nucleus.
• The excitatory input to GP(internal) is lost
• The result is LESS inhibition reaching the VA/VL .
• Thus, the VA/VL is turned up, as is motor cortex, and
there is uncontrollable hyperactivity of the motor system.
Huntington’s chorea
involuntary choreiform movements
show up as rapid, involuntary and purposeless
jerks of irregular and variable location on the
body.
• They are spontaneous and cannot be
inhibited, controlled, or directed by the
patient
• The initial cause of these uncontrollable movements is
the loss of GABAergic cells in the striatum that project
only to GP(external), the head of the indirect pathway.
• Later the striatal cholinergic cells also begin to die.
• It means that VA/VL is turned up, as is the motor cortex,
and there is uncontrollable hyperactivity of the motor
system.
• Both are managed by cholinergic agonist or dopamine
antagonist.
• Some other disorders are basal ganglia:
• Small unilateral lesions of the anteroventral
portion the caudate cause contralateral
choreoathetosis
• Globus pallidus lesions may cause dystonia,
abulia, or akinesia.
basal ganglia motor deficits differ from LMN and
UMN as shown below
THANK YOU

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BASAL GANGLIA

  • 1. BASAL GANGLIA Dr SHANAVAS C DEPT OF NEUROSURGERY, GOVT MEDICAL COLLEGE, KOZHIKODE
  • 2. • Basal ganglia - “Basal nuclei” • Collection of masses of gray matter (subcortical nuclei) situated at the base of forebrain and top of midbrain within each cerebral hemisphere • control of posture and voluntary movement (Contralateral side)
  • 3. Basal Nuclei • Traditionally includes lentiform nucleus, caudate nucleus, claustrum, amygdaloid nucleus. • Functionally includes lentiform nucleus, caudate nucleus, ventral striatum (nucleus accumbens +olfactory tubercle) subthalamic nucleus and substantia nigra.
  • 4. Basal Ganglia 1. Neostriatum Caudate nucleus Putamen Ventral striatum (nucleus accumbens) 2. Paleostriatum Globus pallidus external segment (GPe) Globus pallidus internal segment (GPi) 3. Substantia Nigra Pars compacta (SNc) Pars reticulata (SNr) 4. Subthalamic nucleus (STN)
  • 5. • Lentiform nucleus - Globus pallidus plus putamen • Corpus striatum - Caudate nucleus plus lentiform nucleus • Neostriatum (striatum) - Caudate nucleus plus putamen and ventral striatum (i.e.The nucleus accumbens, along with the nearby olfactory tubercle) • Amygdaloid body - Amygdaloid nucleus
  • 6. • The pallidum (paleostriatum) (globus pallidus ) – a part of the lentiform, which is comprised of a lateral segment ( Gpe) and a medial segment (Gpi). • The medial segment has a midbrain extension known as the reticular part (pars reticulata) of the substantia nigra. The pigmented, compact part (pars compacta) of substantia nigra.
  • 8.
  • 10. • Corpus Striatum • Situated lateral to the thalamus and is almost completely divided by a band of nerve fibers, the internal capsule, into the caudate nucleus and the lentiform nucleus. • “ striatum “ - derived from the striated appearance produced by the strands of gray matter passing through the internal capsule and connecting the caudate nucleus to the putamen of the lentiform nucleus
  • 11. Caudate Nucleus • The caudate nucleus is a large C-shaped mass of gray matter that is closely related to the lateral ventricle and lies lateral to the thalamus. • The lateral surface of the nucleus is related to the internal capsule, which separates it from the lentiform nucleus. • It can be divided into a head, a body, and a tail.
  • 12. • The head of the caudate nucleus is large and rounded and forms the lateral wall of the anterior horn of the lateral ventricle. • The head is continuous inferiorly with the putamen of the lentiform nucleus • The body of the caudate nucleus is long and narrow and is continuous with the head in the region of the interventricular foramen.
  • 13. • The body of the caudate nucleus forms part of the floor of the body of the lateral ventricle • The tail of the caudate nucleus is long and slender and is continuous with the body in the region of the posterior end of the thalamus.
  • 14. • It follows the contour of the lateral ventricle and continues forward in the roof of the inferior horn of the lateral ventricle. • It terminates anteriorly in the amygdaloid nucleus
  • 15. • Lentiform Nucleus • The lentiform nucleus is a wedge-shaped mass of gray matter whose broad convex base is directed laterally and whose blade is directed medially. • It is buried deep in the white matter of the cerebral hemisphere and is related medially to the internal capsule, which separates it from the caudate nucleus and the thalamus.
  • 16. • The lentiform nucleus is related laterally to a thin sheet of white matter, the external capsule, which separates it from a thin sheet of gray matter, called the claustrum. • The claustrum,in turn, separates the external capsule from the subcortical white matter of the insula.
  • 17. • A vertical plate of white matter divides the nucleus into a larger, darker lateral portion, the putamen, and an inner lighter portion, the globus pallidus • The paleness of the globus pallidus is due to the presence of a high concentration of myelinated nerve fibers. • Inferiorly at its anterior end, the putamen is continuous with the head of the caudate nucleus.
  • 18. • Amygdaloid Nucleus • The amygdaloid nucleus is situated in the temporal lobe close to the uncus. The amygdaloid nucleus is considered to be part of the limbic system. • Through its connections, it can influence the body's response to environmental changes. In the sense of fear, for example, it can change the heart rate, blood pressure, skin color, and rate of respiration.
  • 19. • Substantia Nigra and Subthalamic Nuclei • The substantia nigra of the midbrain and the subthalamic nuclei of the diencephalon are functionally closely related to the activities of the basal nuclei. • The neurons of the substantia nigra are dopaminergic and can be excitatory or inhibitory and have many connections to the corpus striatum
  • 20. • The neurons of the subthalamic nuclei are glutaminergic and excitatory and have many connections to the globus pallidus and substantia nigra
  • 21. • Claustrum • The claustrum is a thin sheet of gray matter that is separated from the lateral surface of the lentiform nucleus by the external capsule . Lateral to the claustrum is the subcortical white matter of the insula. The function of the claustrum is unknown
  • 22.
  • 23.
  • 24.
  • 26. • Connections of the Corpus Striatum and Globus Pallidus • The caudate nucleus and the putamen form the main sites for receiving input to the basal nuclei. • The globus pallidus forms the major site from which the output leaves the basal nuclei. • They receive no direct input from or output to the spinal cord.
  • 27. • Connections of the Corpus Striatum • Afferent Fibers 1) Corticostriate Fibers • All parts of the cerebral cortex send axons to the caudate nucleus and the putamen. • Each part of the cerebral cortex projects to a specific part of the caudate-putamen complex. • Most of the projections are from the cortex of the same side.
  • 28. • The largest input is from the sensory-motor cortex. Glutamate (excitatory) is the neurotransmitter of the corticostriate fibers. Thalamostriate Fibers • The intralaminar nuclei of the thalamus send large numbers of axons to the caudate nucleus and the putamen
  • 29. • Nigrostriate Fibers • Neurons in the substantia nigra send axons to the caudate nucleus and the putamen and liberate dopamine at their terminals as the neurotransmitter. • It is believed that these fibers are inhibitory in function.
  • 30. • Brainstem Striatal Fibers • Ascending fibers from the brainstem end in the caudate nucleus and putamen and liberate serotonin at their terminals as the neurotransmitter. • It is thought that these fibers are inhibitory in function
  • 31. • Efferent Fibers • Striatopallidal Fibers • Striatopallidal fibers pass from the caudate nucleus and putamen to the globus pallidus (Gpe) and (Gpi). • They have gamma-aminobutyric acid (GABA) (inhibitory) as their neurotransmitter.
  • 32. • Striatonigral Fibers • Striatonigral fibers pass from the caudate nucleus and putamen to the substantia nigra. • Some of the fibers use GABA or acetylcholine as the neurotransmitter, while others use substance P.
  • 33. • Connections of the Globus Pallidus • Afferent Fibers • Striatopallidal Fibers • As explained above • Efferent Fibers • Pallidofugal Fibers • Pallidofugal fibers are complicated and can be divided into groups: • (1) the ansa lenticularis, which pass to the thalamic nuclei.
  • 34. • (2) the fasciculus lenticularis, which pass to the subthalamus; • (3) the pallidotegmental fibers, which terminate in the caudal tegmentum of the midbrain; and • (4) the pallidosubthalamic fibers, which pass to the subthalamic nuclei
  • 35.
  • 36.
  • 37. VENOUS DRAINAGE • The deep cerebral veins drain the corpus striatum, thalamus, and choroid plexuses. • A thalamostriate vein drains the thalamus and caudate nucleus. Together with a choroidal vein, it forms the internal cerebral vein. The two internal cerebral veins unite beneath the corpus callosum to form the great cerebral vein (of Galen).
  • 38.
  • 39. Functional organisation of basal ganglia and other pathaways • The basal ganglia has dense internuclear connections. • Five parallel and separate closed circuits through the basal ganglia have been proposed. • These are the motor, oculomotor, dorsolateral prefrontal, lateral orbitofrontal, and limbic loops (Rodriguez-Oroz et al., 2009 )
  • 40. • It is now generally agreed that these loops form three major divisions— sensorimotor, associative, and limbic—that are related to motor, cognitive, and emotional functions, respectively
  • 41.
  • 42.
  • 43. • Within each basal ganglia circuit lies an additional level of complexity. • Each circuit contains two pathways by which striatal activity is translated into pallidal output.
  • 44. • These two pathways are named the direct and indirect pathways, depending on whether striatal outflow connects directly with the GPi or first traverses the GPe and STN before terminating in the GPi. • The direct and indirect pathways have opposite effects on outflow neurons of the GPi and SNr.
  • 45.
  • 46. • In the motor direct pathway, excitatory neurons from the cerebral cortex synapse on putamenal neurons, which in turn send inhibitory projections to the GPi and its homolog, the SNr. • The GPi/SNr sends an inhibitory outflow to the thalamus
  • 47. • Activity in the direct pathway disinhibits the thalamus, facilitating the excitatory thalamocortical pathway and enhancing activity in its target, the motor cortices. • Thus, the direct pathway constitutes part of an excitatory cortical-cortical circuit that likely functions to maintain ongoing motor activity
  • 48.
  • 49. • In the indirect pathway, excitatory axons from the cerebral cortex synapse on putaminal neurons. • These neurons send inhibitory projections to the GPe, and the GPe sends an inhibitory projection to the STN.
  • 50. • The net effect of these projections is disinhibition of the STN. The STN in turn has an excitatory projection to the Gpi. • Activity in the indirect pathway thus excites the GPi/SNr, which in turn inhibits the thalamocortical pathway. • Thus, the net effect of increased activity in the indirect pathway is cortical inhibition.
  • 51.
  • 52. • DOPAMINERGIC and CHOLINERGIC Modulation of Direct and Indirect Pathways • DOPAMINE is produced by cells in the pars compacta of the substantia nigra (SNc). • Nigrostriatal axon terminals release dopamine into the striatum. • Dopamine has an EXCITATORY effect upon cells in the striatum that are part of the Direct Pathway, via D1 receptors.
  • 53. • Dopamine has an INHIBITORY effect upon striatal cells associated with the Indirect Pathway, via D2 receptors • Both of these effects lead to increased motor activity
  • 54. • Cholinergic (Ach) interneurons synapse on the GABAergic striatal neurons that project to GPi AND on the striatal neurons that project to GPe. • The cholinergic actions INHIBIT striatal cells of the Direct pathway and EXCITE striatal cells of the Indirect pathway. • Thus the effects of ACh are OPPOSITE the effects of dopamine on the direct and indirect pathways and decrease motor activity.
  • 55.
  • 56.
  • 57. • Functions of motor loop: • They seem to be involved in scaling the strength of muscle contractions and, in collaboration with SMA, in organizing the requisite sequences of excitation of cell columns in the motor cortex. • They come into action after the corticospinal tract has already been activated by ‘premotor’ areas including the cerebellum.
  • 58. • it is believed that the putamen provides a reservoir of learned motor programs which it is able to assemble in appropriate sequence for the movements decided upon, and to transmit the coded information to SMA
  • 59. • Cognitive loop (prefrontal) • The head of the caudate nucleus receives a large projection from the prefrontal cortex, and it participates in motor learning. • The VA nucleus completes an ‘open’ cognitive loop through its projection to the premotor cortex, and a ‘closed’ loop through a return projection to the prefrontal cortex.
  • 60. • The cortical connections of the caudate suggest that it participates in planning ahead, particularly with respect to complex motor intentions.
  • 61. • Limbic loop: • This loop passes from inferior prefrontal cortex through nucleus accumbens (anterior end of the striatum) and ventral pallidum, with return via the mediodorsal nucleus of thalamus to the inferior prefrontal cortex.
  • 62. • The limbic loop is likely to be involved in giving motor expression to emotions, e.g. through smiling or gesturing, or adoption of aggressive or submissive postures. • The loop is rich in dopaminergic nerve endings, and their decline may account for the mask-like facies and absence of spontaneous gesturing characteristic of Parkinson’s disease, and for the dementia which may set in after several years.
  • 63. • Oculomotor loop: • The oculomotor loop commences in the frontal eye field and posterior parietal cortex (area 7). It passes through the caudate nucleus and through the reticular part of the substantia nigra (SNpr). • It returns via the ventral anterior nucleus of the thalamus to the frontal eye field and prefrontal cortex.
  • 64. • SNpr sends an inhibitory GABAergic projection to the superior colliculus, where it synapses upon cells controlling automatic saccades. • These cells are also supplied directly from the frontal eye field
  • 65. • While the eyes are fixated, SNpr is tonically active. Whenever a deliberate saccade is about to be made toward another object, the oculomotor loop is activated and the superior colliculus is disinhibited. • In PD oculomotor hypokinesia is due to faulty disinhibition of the superior colliculus following associated neuronal degeneration within SNpr.
  • 66. Disorders of basal ganglia Hyperkinetic disorders • excess direct pathway output • insufficient indirect pathway output • seen with chorea, athetosis, and ballism Hypokinetic disorders • insufficient direct pathway output • excess indirect pathway output
  • 67. • Parkinson disease includes both types of motor disturbances. • classically described as triad of rigidty, bradykinesia, tremor • dopaminergic neurons in substantia nigra pars compacta are lost in Parkinson’s disease. • The degenerating nigral dopaminergic cells accumulate deposits of protein called Lewy Bodies.
  • 68. • The SN lesion takes away the dopaminergic drive on the direct pathway at the same time ACh interneurons are still inhibiting the striatal cells at the head of the direct pathway leads to double inhibition of direct pathway and less active cortex.
  • 69. • a STN lesion increases activity in the indirect pathway, which turns DOWN motor activity • This results in hypokinetic symptoms such as akinesia (no movement) or bradykinesia (slow movement) • In PD, rigidity is present in all muscle groups, both flexor and extensor, leads to cog wheel and lead pipe rigidity
  • 70. • Normally, both corticospinal and reticulospinal fibers are tonically facilitatory to 1b inhibitory internuncials. • In PD, activation of the primary motor cortex by SMA is known to be both reduced and oscillatory, thus accounting for the pronounced effects in the forearm and hand.
  • 71. • Impaired reticulospinal activity is more likely to be significant with respect to the lower limbs • This explains rigidity and static tremors ( 3-6 hz) in PD. • Treatment of PD • Hypokinetic pt are treated with dopamine agonist like L-dopa or drugs that decrease the level of Ach in the striatum.
  • 72. • Parkinson’s disease can be reduced or alleviated by placing stimulating electrodes in the thalamus, subthalamic nucleus, or pallidum • Thalamic stimulators seem to be effective in reducing tremor, but do little for akinesia. • Pallidal stimulation seems to have a more all- encompassing therapeutic effect
  • 73. • Pallidotomy also shown some improvement parkinsonian features
  • 74. • Two classic hyperkinetic disorders are hemiballism and Huntington’s chorea
  • 75. Hemiballism • characterized by wild, flinging movements of the body • results from lesion in the subthalamic nucleus. • The excitatory input to GP(internal) is lost • The result is LESS inhibition reaching the VA/VL . • Thus, the VA/VL is turned up, as is motor cortex, and there is uncontrollable hyperactivity of the motor system.
  • 76. Huntington’s chorea involuntary choreiform movements show up as rapid, involuntary and purposeless jerks of irregular and variable location on the body. • They are spontaneous and cannot be inhibited, controlled, or directed by the patient
  • 77. • The initial cause of these uncontrollable movements is the loss of GABAergic cells in the striatum that project only to GP(external), the head of the indirect pathway. • Later the striatal cholinergic cells also begin to die. • It means that VA/VL is turned up, as is the motor cortex, and there is uncontrollable hyperactivity of the motor system. • Both are managed by cholinergic agonist or dopamine antagonist.
  • 78. • Some other disorders are basal ganglia: • Small unilateral lesions of the anteroventral portion the caudate cause contralateral choreoathetosis • Globus pallidus lesions may cause dystonia, abulia, or akinesia.
  • 79. basal ganglia motor deficits differ from LMN and UMN as shown below