Transcript L26-Basal Ganglia Lecture Oct 6 2013

PHYSIOLOGY OF BASAL GANGLIA
Prof. Sultan Ayoub Meo
MBBS, M.Phil, Ph.D (Pak), Med Ed, Med Ed, (Dundee),
FRCP (London), FRCP (Dublin), FRCP (Glasgow), FRCP (Edinburgh)
Prof. Department of Physiology
College of Medicine, King Saud University
Lecture Objectives
• Enumerate different nuclei of basal ganglia
• Know different neurotransmitters that have a role
in basal ganglia functions
• Appreciate general functions of basal ganglia
• Physiological basis of basal ganglia disorders
BASAL GANGLIA: NUCLEI
Five nuclei :
 Caudate Nucleus
 Putamen
 Globus Pallidus – external & internal segments.
 Subthalamic Nucleus
 Substantia Nigra- pars compacta,reticulata
Basal ganglia: A group of nuclei, act as a unified functional unit.
Basal ganglia: A subcortical nuclei of grey matter located in the interior part of
cerebrum / base of the forebrain
connected with cerebral cortex, thalamus, and other brain areas.
Play a role in action selection, decision of possible behaviors to execute at a given time
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BASAL GANGLIA: NUCLEI
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BASAL GANGLIA: NUCLEI
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Basal ganglia Input
1. Parietal cortex (primary and secondary
somatosensory information, secondary visual
information),
2. Temporal cortex (secondary visual and
auditory information),
3. Cingulate cortex (limbic and emotional status
information),
4. Frontal cortex (primary and secondary motor
information),
5. Prefrontal cortex.
Basic Circuits of basal ganglia
Motor loop (putamen circuit): Learned moment.
Cognitive loop (Caudate circuit): Cognitive control of sequences
of motor pattern. Mainly it is concerned with motor intentions.
(Cognition means thinking process using sensory input with
information already stored in memory.)
Limbic loop: Giving motor expression to emotions like, smiling,
aggressive or submissive posture.
Occulomotor loop: Voluntary eye movement (saccadic movement)
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Motor loop (putamen circuit): Concerned with learned
moment. Putamen circuit is inhibitory. Executes skilled motor
activities for example cutting paper with a scissor, hammering on
nail, shooting a basket ball & like throwing a base ball.
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Cognitive loop (Caudate circuit): Concerned with
cognitive control of sequences of motor pattern.
Motor intentions (Cognition means thinking process using
sensory input with information already stored in memory)
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Neurotransmitters of basal
ganglia
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Neurotransmitters of basal
ganglia
Dopamine pathway: From substantia nigra to caudate
nucleus and putamen.
Gama amino butyric acid pathway: From caudate nucleus
and putamen to globus pallidus and substantia nigra.
Acetylcholine pathway: From cortex to the caudate nucleus
to putamen.
Glutamate: Provide the excitatory signals that balance out the
large no. of the inhibitory signals transmitted specially by the
dopamin, GABA & serotonin inhibitory transmitters.
Dopamine: excites areas of caudate/putamen with D1 receptors to promote
the direct pathway, inhibits areas of caudate/putamen with D2 receptors to
inhibit the indirect pathway
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Dopamine: Neuromodulatory neurotransmitter, excites areas
of the caudate/putamen with D1 receptors to promote the
direct pathway, inhibits areas of the caudate/putamen with
D2 receptors to inhibit the indirect pathway
Glutamate: Excitatory neurotransmitter
Subthalamic nucleus projects glutamate to stimulate the
ventrolateral thalamus. Ventrolateral thalamus projects
glutamate to stimulate the primary localized motor cortex
GABA: Inhibitory neurotransmitter:
Caudate/Striatum (direct) projects GABA to inhibit the Gpi
GPi projects GABA to inhibit the ventrolateral nucleus
Caudate/Striatum (indirect) projects GABA to inhibit the GPe
GPe projects GABA to inhibit the subthalamic nucleus
Direct
Excitatory
Cerebral cortex
Prefrontal, premotor,
primary motor area,
somatosensory area
Thalamus
Thalamus
Caudate
nucleus
Indirect
Inhibitory
Putamen
Via globus
pallidus
subthalamic
nucleus 14
RED: Excitatory glutamatergic pathways,
BLUE: Inhibitory GABAergic pathways,
Magenta: Modulatory dopaminergic pathways
GPe: globus pallidus external; GPi: globus pallidus internal; STN: subthalamic
nucleus; SNc: substantia nigra compacta; SNr: substantia nigra reticulata
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Cortex (stimulates) → Striatum (inhibits) → "SNr-GPi"
complex (less inhibition of thalamus) → Thalamus
(stimulates) → Cortex (stimulates) → Muscles, →
(hyperkinetic state)
Cortex (stimulates) → Striatum (inhibits) → GPe (less
inhibition of STN) → STN (stimulates) → "SNr-GPi"
complex (inhibits) → Thalamus (stimulating less) →
Cortex (stimulating less) → Muscles, → (hypokinetic state)
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FUNCTIONS OF BASAL GANGLIA

Voluntary motor activities

Regulatory

Procedural learning

Routine behaviors (Habits)
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FUNCTIONS OF BASAL GANGLIA
2. Regulatory
1.Voluntary motor activities
Plan, Programming
Cognitive (thinking)
Initiate
Emotional functions
Maintain (Tone)
Voluntary control of eye movement
3. Procedural learning
4. Routine behavior ( habits)
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Functions
1. Planning & programming (discharge before
movement begins ) .
2. Motor control of the final common pathway .
3. Muscle tone (lesion increases).
4. Cognitive functions (Frontal cortex) Lesions disrupt
performance .
5. Speech , lesion of left caudate results in disturbed
speech dysarthria .
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Metabolic characteristics


High Copper content .
Wilsons disease (Copper intoxication):
Ceruloplasmin is low,
Lenticular degeneration .
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Disorders of movement in Basal
ganglia disease
1. Hyperkinetic: Excessive abnormal movement i.e.
chorea, athetosis, ballism
2. Hypokinetic: Slow movements i.e. akinesia,
bradykinesia .
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HYPERKINESIA
Chorea: Rapid involuntary “ dancing” movements
Athetosis: Continuous , slow writhing movements .
Ballism (Hemiballismus): Involuntary flailing ,
intense and violent movements
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HYPOKINESIA
Akinesia: Difficulty in initiating movement
Braykinesia :Slowness of movement .
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Parkinson’s disease: Paralysis Agitans
Parkinson
1. Slow degeneration / loss of dopaminergic
nigrostriatal neurons (60-80 %).
2. Phenthiazines(tranquilizers drugs) .
3. Methyl-Phenyl-Tetrahydro-Pyridine
Toxic to SN.
(MPTP).
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Features
Tremors: The tremor most apparent at rest
Rigidity: Simultaneous contraction of flexors and
extensors, which tends to lock up the limbs. Rigidity
agonists and antagonists ( spacticity). Lead-pipe rigidity;
cogwheel -catches (mixture of tremer and rigidity)
Akinesia –Bradykinesia: Movements (swinging of arms
during walking. Facial expression is masked.
Bradykinesia, or "slow movement", is a difficulty
initiating voluntary movement, as though the brake
cannot be released
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Features
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Pathogenesis
Excitation imbalance Inhibition
loss of dopamine inhibition of putamen
increases in inhibitory output to GBes
decreases inhibitory output of STN
increases excitatory output GBis
increases inhibitory output to thalamus
reduces excitatory drive to cerebral cortex
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Parkinson’s Disease:
Treatment(FYI)

Drug Therapy


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

L-DOPA
Cholinergic
Pallidectomy
Electrical stimulation of Globus pallidus
Tissue transplants
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Huntington’s Disease (Chorea)

Rare

onset 30-40s


Degeneration of Striatum



early as 20s
Caudate
Putamen
GABA & ACh neurons
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Huntingtons Disease
Hereditary , autosomal dominant .
Disease of caudate & putamen.
Jerky movement of hands toward end of reaching an
object .
Chorea
Slurred speech and incomprehensive.
Progressive Dementia
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Huntingtons Disease
Loss of GABA – Cholinergic neurons .
Loss of GABAergic neurons leads to chorea
Loss of Dopaminergic neurons leads to Parkinson's
disease .
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Summary of functions of basal ganglia

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It play important motor function in starting and stopping
motor functions and inhibiting unwanted movement.
It changes the timing and scales the intensity of
movements.
Putamen circuit is inhibitory. Executes skilled motor
activities for example cutting paper with a scissor,
hammering on nail, shooting a basket ball & like throwing
a base ball.
Putamen circuit has indirect connection to cortex via
thalamus. while caudate has direct connection to the
cortex from thalamus.
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Summary of functions of basal ganglia
Caudate circuit is excitatory, has instinctive function
which works without thinking and need quick response.
eg. response after seeing a lion.
[Note: effects of basal ganglia on motor activity are
generally inhibitory.]
Lesions of the basal ganglia produce effects on contra
lateral side of the body
Damage to basal ganglia does not cause paralysis.
However it results in abnormal movements
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