Basal Ganglia

Question 1

what is the hierarchy of motor control

Answer 1

• motor cortex
  
  • direct motor output
  • corticospinal tract
  • damage causes paralysis and/or spasticity
• cerebellum
  
  • modulates movement accuracy
  • receives afferent information from spinal cord
  • projects to sensorimotor areas of cortex
  • damage results in inaccurate / poorly timed movement (e.g. atoxia)
• basal ganglia
  
  • strategic aspects of movement
  • no direct connections to spinal cord
  • reciprocal connections to almost all areas of cerebral cortex
  • damage results in problems initiating and terminating movement

Question 2

what is the cortex loop

Answer 2

• basal ganglia connections
  
  • widespread reciprocal connections to cerebral cortex (via thalamus)
  • not just involved in movement
  • behaviour and emotion
• cerebellum connections
  
  • connections only to sensorimotor areas of cerebral cortex (via thalamus)
  • receives input from brainstem and spinal cord
  • involved almost exclusively with movement

Question 3

what is the gross anatomy of the basal ganglia

Answer 3

• the basal ganglia is a collection of 5 nuclei:
  
  • caudate
  • putamen
  • globus pallidus
    
    • internal (GPi)
    • external (GPe)
  • subthalamic nucleus (STN)
  • substantia nigra
    
    • pars compacta (SNc)
    • pars reticulata (SNr)
• caudate and putamen are part of the striatum

Question 4

what are the inputs

Answer 4

• striatum (caudate and putamen)
• receives direct and indirect (via thalamus) connections from cerebral cortex

Question 5

what are the internal connections

Answer 5

• striatum projects to:
  
  • globus pallidus (striatopallidial pathway)
  • substantia nigra (striatonigral pathway)
• STN forms indirect pathway between GPe and SNr
• GPi and SNr are the output centre of the basal ganglia and send inhibitory signals to the thalamus

Question 6

what are the outputs

Answer 6

• GPi and SNr
• provide tonic inhibitory output to thalamus

Question 7

what inputs and outputs make up the feedback loop

Answer 7

• basal ganglia receives excitatory input from cerebral cortex which then sends inhibitory signals to the thalamus in turn suppressing motor cortical activity
• excessive basal ganglia input results in slow movement and reduced input results in enhanced movement

Question 8

what inputs and outputs make up the cortical loop

Answer 8

• the cerebral cortex, basal ganglia and thalamus form a transcortical loop comprising 3 stages
  
  • striatum (putamen) receives vast array of inputs from the cerebral cortex (motor and sensory)
  • output from GPi and SNr project to thalamus (inhibitory signal)
  • inhibited thalamus projects to motor cortex, thus suppressing movement

Question 9

what is the effect of dopamine on the striatum

Answer 9

• dopamine originates from SNc
  
  • effects may be excitatory or inhibitory depending upon the receptor it binds to
• dopamine has opposite actions in the direct and indirect pathways
  
  • excites direct pathway (D1R)
  • inhibits indirect pathway (D2R)
• both effects disinhibit thalamic output thereby facilitating movement

Question 10

what are the direct and indirect motor pathways

Answer 10

• tonic inhibitory output from basal ganglia to thalamus
• neurotransmitters
  
  • excitatory (glutamate, open arrows)
  • inhibitory (GABA, filled arrows)
  • mixed (dopamine, mixed arrows)
• STN is a relay from the striatum (input) to the GPi / SNr (output), forming an indirect motor pathway
• direct pathway involves two inhibitory synapses resulting in disinhibition, thereby facilitating movement
• indirect pathway involves excitation of the inhibition, thereby suppressing movement

Question 11

what is the basal ganglia pathology

Answer 11

• basal ganglia disorders can be explained by an imbalance between the action of direct versus indirect pathways
  
  • Parkinson’s:
    
    • increased activation of indirect pathway (inhibitory) and decreased activation of direct pathway (excitatory)
    • movement is therefore suppressed
  • Huntington’s:
    
    • decreased activation of indirect pathway (inhibitory) and increased activation of direct pathway (excitatory)
    • movement is facilitated

Question 12

what is Parkinson’s disease

Answer 12

• affects ~1% of individuals over 50 years of age
• loss of dopaminergic cells in substantia nigra
• increases tonic inhibitory output of basal ganglia
• symptoms include:
  
  • bradykinesia (slow movement)
  • akinesia (inability to initiate movement)
  • rigidity (increased muscle tone)
  • tremor
  • postural instability (stooped posture, right)
• treatments include:
  
  • deep brain stimulation (disrupts function of STn, inhibits indirect pathway, thereby inhibiting thalamic inhibitor)

Question 13

do Parkinson’s patients lack dopamine

Answer 13

PET scans shows reduced dopamine uptake in putamen

Question 14

what is Huntington’s disease

Answer 14

• rapid, jerky motions with no clear purpose (choreiform = dancelike)
• patients often try to integrate these motions into more purposeful movements
• caused by mutation of the Huntington gene resulting in selective atrophy of striatum
• decreases activation of indirect pathway (inhibitory) resulting in movement facilitation

Question 15

quick summary of basal ganglia disease mechanisms

Answer 15

• Parkinson’s disease = hypokinetic
  
  • loss of dopaminergic cells from substantia nigra
  • overactive indirect pathway, underactive direct pathway
  • increased inhibition of thalamus
  • less movement
• Huntington’s disease = hyperkinetic
  
  • atrophy of striatum
  • underactive indirect pathway
  • decreased inhibition of thalamus
  • more movement