Modulation of Movement by the Basal Ganglia

Question 1

Describe Basal ganglia basics & Anatomy

Answer 1

1. Responds in anticipation of and during movements
2. Helps to focus “desired” movement while inhibiting “undesired” movements
3. Links cortex with upper motor neurons in primary cortex, premotor areas, and brainstem
4. Influences movement by acting on upper motor neurons

Question 2

Name the SIX key areas of the Basal Ganglia

Answer 2

1. Straitum (Caudate, Putamen)
2. Globus Pallidus (GP)
   External (lateral) = GPe
   Internal (medial) = Gpi (Output)
3. Subthalamic Nucleus
4. Substantia Nigra (SN) (midbrain)
   SN pars compacta (input) = SNc
   SN pars reticulata (output) = SNr
5. Thalamus
   Ventro-anterior and
   Ventro-lateral nuclei (VA/VL) (Complex of Thalamus)
6. Motor Cortex

Question 3

Give Specifics about the Caudate/Putamen

Answer 3

1. Caudate/Putamen receive input from outside the Basal Ganglia
2. Destination neurons in caudate/putamen = Medium Spiny Neurons

Question 4

Caudate/Putamen ALSO receives input from WHERE?

Answer 4

D. Substantia nigra pars compacta (SNc)
Projections
- SNc (Dopamine, D1, excitatory +) to Caudate/Putamen
- SNc (Dopamine, D2, inhibitory -) to Caudate/Putamen

Question 5

Describe Projections “TO” the Basal Ganglia

Answer 5

• Basal Ganglia receives most projections from cerebral cortex
• Major input zone: Caudate/Putamen
• Cortex (glut, excitatory) to striatum
• Straitum also receives brainstem input from substantia nigra pars compacta
  Projections:
  SNc (D1, excitatory + ) to Caudate/Putamen
  SNc (D2, inhibitory - ) to Caudate/Putamen

Question 6

Projections “TO”:

Give specifics about Medium Spiny Neurons

Answer 6

1. Large dendritic trees

2. GABAergic (inhibitory -)

Question 7

Projections “WITHIN” the Basal Ganglia:

Describe.

Answer 7

1. Caudate/Putamen to Globus Pallidus (GP).
   Caudate/Putamen (Gaba, inhibitory) to GPi
   Caudate/Putamen (GABA, inhibitory) to GPe
2. GPe (GABA, inhibitory -) to Subthalamic Nucleus (STN)
3. STN (Glutamate, excitatory +) back to GPi

Question 8

Projections “FROM” the Basal Ganglia:

Describe:

Answer 8

Output Area

 - - Substantia Nigra pars reticulata (SNr)
 - - Globus Pallidus internal (GPi)

To motor cortex
– Via ventral anterior and ventral lateral nuclei of thalamus (VA/VL)

Forms Loop!

Question 9

Projections “FROM” the Basal Ganglia:

Describe D. Substantia Nigra pars reticulata (SNr)

Answer 9

Caudate/Putamen (GABA, inhibitory - ) to SNr to (GABA, inhibitory - ) Superior Colliculus (to prevent unwanted saccades)

Question 10

Projections “FROM” the Basal Ganglia:

Describe B. Globus Pallidus internal (GPi)

Answer 10

• GPi (GABA, inhibitory - ) to Thalamus

- Thalamus (Glutamate, excitatory + ) to Frontal Cortex

Question 11

Circuits of Basal Ganglia:

Describe Direct and Indirect Pathway

Answer 11

Center surround organization of 
direct/indirect pathways

Direct Pathway

• Input from cortex and SN (both glut, excit) goes to caudate/putamen and then directly to (GABA) GPi.
  - GPi goes to (GABA) thalamus and then to (Glut) PREmotor cortex
• Dopamine, D1, Excitatory
• Activate intended movement

Indirect Pathway

• Indirect from caudate/putamen to GPe to STN to GPi
• Dopamine, D2, Inhibitory
• Antagonizes activity of direct pathway

Question 12

Describe how Dopamine Modulates Basal Ganglia Circuits

Answer 12

1. Dopaminergic cells in SN pars compacta, SNc

2. Effect of dopamine is determined by types and location of receptors

Question 13

Metabotropic Receptors- GPCR:

Describe

Answer 13

1. Neurotransmitter binds
2. G-protein is activated
3. G-protein subunits or intracellular messengers modulate ion channels
4. Ion channel opens
5. Ions flow across membrane

Question 14

Describe Dopamine’s effect on Striatum (cAMP, G-protein subunits…)

Answer 14

1) Facilitate activity of DIRECT pathway via D1 receptors. D1 increases cAMP, enhance excitatory inputs
2) Reduce activity of INDIRECT pathway via D2 receptors. D2 decreases cAMP, negate excitatory inputs
3) Same outcome: increase thalamic output activity and both will increase movement

Question 15

Identify and Describe Hypokinetic and Hyperkinetic movement disorders

Answer 15

Hypokinetic:

• Parkinson’s Disease
• Loss of nigrostriatal dopaminergic neurons
• Thalamic activation of upper motor neurons decreased

Hyperkinetic:

• Hungtington’s Disease
• Medium spiny neurons projecting to GPe degenerate
• Lose restraining influence of basal ganglia

Question 16

Describe Specifics of Parkinson’s Disease

Answer 16

1. Loss of nigrostriatal dopaminergic neurons
2. Key signs:
   
   • diminished facial expressions
   • lack associated movements (swinging arms during walking)
   • movement is difficult to initiate
   • if initiated, it is difficult to terminate
3. Failed dis-inhibition of basal ganglia
4. Thalamic activation of upper motor neurons decreased

Question 17

Give Therapeutic Approaches for Parkinson’s Disease

Answer 17

1. Distribution of degenerating neurons is largely restricted to substantia nigra
2. Treatment options
   - gene therapy: implant cells genetically modified to express TH, key enzyme to convert L-DOPA to dopamine
   - stem cells?
   - Supplementation or imitation of Dopamine
   - Surgically lesion STN or GPi to correct for imbalance
   - Deep brain stimulation

Question 18

Describe Huntington’s Disease

Answer 18

• • CAG repeats
• • Loss of medium spiny neurons projecting to GPe
• • No inhibition on GPe  GPe becomes abnormally active
• • Decrease excitatory subthalamic nucleus output to GPi
• • Less GPi output = less restraining influence
• • Key signs:
    
    • choreiform movement
    • hemiballismus (can occur with damage to STN)