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Physiopathology – Movement disorders
Prof. Gregor Rainer, Ph.D.
Brain structures involved in motor control
Basal Ganglia pathways
Dopamine
Striatum (Caudate and Putamen)
Basal Ganglia: direct pathway
Striatum activity
Striatum GPi, SNr
Thalamus activity
Disinhibition
Basal
Ganglia
Movement
Excitatory
Inhibitory
Basal Ganglia: indirect pathway
Basal
Ganglia
Striatum GPe
Disinhibition
Striatum activity
Thalamus activity
Movement
Excitatory
Inhibitory
Direct and indirect pathways
Basal ganglia
input to cortex -ve +ve
Indirect
pathway Direct
pathway balance
promotes
movement
attenuates
movement
Glutamate
GABA
Dopamine
Basal Ganglia: neurotransmitters
D1
D2
Direct and indirect pathways
Basal ganglia
input to cortex -ve +ve
Indirect
pathway Direct
pathway balance
promotes
movement
attenuates
movement
Parkinson´s disease
-ve +ve
Indirect
pathway
Direct
pathway
-ve +ve
Indirect
pathway
Direct
pathway
Normal Parkinson’s
Basal ganglia
input to cortex
Basal ganglia
input to cortex
Parkinson’s
disease
• Hypokinetic disorder
• Resting tremor, Muscle stiffness, Bradykinesia (slowness of movements)
• Cognitive decline (e.g. depression, insomnia)
• Dopamine levels reduced by degeneration of substantia nigra pars compacta, MPTP
Glutamate
GABA
STN Stimulation in Parkinson‘s disease
• Deep brain stimulation-activate?
• This should further enhance the indirect pathway
• Stimulation at high frequencies actually reduces STN activity
• Reduces indirect pathway
• Mechanism still not completely understood – Basic Research needed
Glutamate
GABA
Deep brain stimulation: surgery
Deep brain stimulation: patient report
2:18
Huntington´s disease
Indirect
pathway
Direct
pathway
-ve +ve
Indirect
pathway
Direct
pathway
Huntington’s
disease
• Hyperkinetic, hereditary disorder
• Uncontrolled movement (Chorea), Fidgetting, clumsiness, falls
• Cognitive decline (Absent mindedness, irritability, depression)
• Increased activity in Dopamine neurons.
Glutamate
GABA
