Making Things Happen - 2 Motor Disorders

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Making Things Happen - 2Motor Disorders

• How Your Brain Works - Week 7
• Dr. Jan Schnupp
• jan.schnupp_at_dpag.ox.ac.uk
• HowYourBrainWorks.net

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Subcortical Motor Structures
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The Basal Ganglia

• GPi globus pallidus internal segment
• GPe globus pallidus external
• STN subthalamic nucleus
• Sub Nig Substantia Nigra (pars compacta)

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The Motor Loop

• Excitatory (Glutamatergic) connections shown in
  dark green
• Inhibitory (GABAergic) connections shown in red
• Dopaminergic connections shown in sky blue

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Parkinsons Disease

• The cause of Parkinsons disease is a
  degeneration of dopaminergic neurons in the
  substantia nigra pars compacta

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Dopamine BiosynthesisandL-DOPA
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Why Substantia Nigra neurons are black
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Parkinsonian Tremor Bradykinesia

• http//www.youtube.com/watch?vjclJVrLODQA

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Parkinsonian Gaitand L-DOPA treatment

• http//www.youtube.com/watch?vsf1N0Zf5IqA

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Dyskinesia

• A common side-effect of L-DOPA therapy
• The case shown here is quite severe

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Michael Fox backs stem cell research
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Cell Differentiation
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MPPP and MPTP

• MPPP is a synthetic heroin substitute
• MPTP is a contaminant that can arise from MPPP
  synthesis. It kills dopaminergic neurons and
  makes people (or animals) instantly Parkinsonian.
• Some successes have been reported in treating
  MPTP poisoned addicts with embryonic tissue
  grafts.

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Break
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Deep Brain Stimulation

• DBS most commonly targets the subthalamic nucleus

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Treating Parkinsonian Tremor with DBS

• http//www.youtube.com/watch?vg5Y9f4Xr42o

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Dystonia before and after DBS
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Huntingtons Disease

• A genetic mutation of the HTT gene on chromosome
  4 causes premature neural cell death in
  homozygous carriers.
• Spiny stellate neurons projecting from putamen to
  the GPe are the first affected.
• As the disease progresses, damage is more
  widespread.

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Motor Related Areas of Cortex
Supplementary
Motor Area
Frontal Eye
Fields
Primary Motor
Cortex
Somatosensory
Somatosensory
Somatosensory
Cortex
Cortex
Cortex
Brocas Area
Premotor Area
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The Forebrain Loops Upon Loops
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Mesolimbic Mesocortical Dopamine Pathways
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Huntingtons Chorea
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Reported prevalences of behavioural and
psychiatric symptoms in Huntington's disease
Irritability 3873
Apathy 3476
Anxiety 3461
Depressed mood 3369
Obsessive and compulsive 1052
Psychotic 311
Reported prevalences of behavioral and
psychiatric symptoms in Huntington's disease10
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Dopaminergic Antagonists

• Dopamine
• Chlorpromazine

• Numerous dopamine antagonists are used to treat
  diseases including obsessive-compulsive disorder,
  Tourettes syndrome, anxiety disorders and
  psychotic states.
• Parkinson-like symptoms are common side effects.

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A Look Ahead

• Todays lecture revolved around the role of
  tonic Dopamine levels as a sort of thermostat
  of activity levels in motor, cognitive and limbic
  loops around the brain.
• However, the activity of dopaminergic neurons in
  the SN and VTA also changes in a phasic manner
  that appears to predict how rewarding a
  particular activity is likely to be.