Lecture 11 - Motor control and disorders of action (P2)

Question 1

Basal ganglia motor circuit

Answer 1

the loops connecting the BG and thalamus consist of a mix of inhibitory + excitatory connections that combine to form complementary routes

Question 2

the input and output structure of the BG

Answer 2

input: PUTAMEN - receives inputs from cortical areas (striatum)
output: globus pallidus medial segment (GPm) projects back to motor cortex.

Question 3

direct pathway of the BG circuit

Answer 3

• excitatory pathway

1. excitatory signal from cortex
2. increased inhibitory signal from putamen to GPm
3. reduced inhibitory signal from GPm to thalamus
4. increased excitatory signal from thalamus to motor cortex.

• this pathway releases the movement (promotes action)

Question 4

indirect pathway:

Answer 4

this is inhibitory

1. increased inhibitory signal from putamen to GP lateral segment (GPL)
2. reduced inhibitory signal from GPL to STN
3. increased excitatory input to GPm
4. increased inhibitory output to thalamus
5. reduced excitatory output to cortex

this pathway inhibits action

Question 5

gain control?

Answer 5

BG acts as a gain control:

direct pathway - allows desired movements to occur
indirect pathway - prevent undesired movements

Question 6

Parkinsons disease - and the BG circuity pathway

Answer 6

lack of dopamine has opposing effects on 2 pathways:

1. increase output of indirect pathway (the brakes)
2. decrease output of direct pathway (the acceleration)

this is due to the increase in GPm activity

both these pathways lead to INCREASED INHIBITION OF THE THALAMUS AND REDUCED EXCITATION OF THE CORTEX

Question 7

Motor symptoms of Parkinsons

Answer 7

• akinesia (lack of spontaneous movement)
• bradykinesia (slowness)
• decay of movement sequences (shuffle)
• failure to scale muscle activity to movement amplitude
• failure to wed several movement components into a single action plan rigidity
• tremor

Question 8

Parkinson’s treatment

Answer 8

• L-dopa (dopamine agonist)
• surgery
• DBS on SMA, GP and thalamus

Question 9

hypokinetic versus hyperkinetic

Answer 9

hypokinetic: reduction in movement
hyperkinetic: increase in movement

Question 10

Huntington’s Disease

Answer 10

• inherited
• autosomal dominant condition
• onset in 30s/40s
• causes CHOREA - uncontrolled movements
• degeneration of putamen and caudate

Question 11

Huntington’s Disease

Answer 11

• inherited
• autosomal dominant condition
• onset in 30s/40s
• causes CHOREA - uncontrolled movements
• degeneration of putamen and caudate

Question 12

HD and the BG circuit - why does HD arise

Answer 12

HD arises because of the depletion of inhibitory neurons in the early part of the indirect pathway l linking the BG with the thalamus

• interactivity of indirect pathway:
  - reduced inhibition of GPL
  - increased inhibition of STN
  - reduced activity of GPm

too much movement as a result

Question 13

cognitive impairments of HD

Answer 13

problems with:

• attention
• executive function
• speed of processing
• prospective memory
• emotion recognition

Question 14

Tourette Syndrome

Answer 14

• hyperkinetic
• simple tics e.g. blinking
• complex tics e.g. gestures

increases with stress

• hereditary
• links to obsessive-compulsive behaviour
• 4x more common in boys

Question 15

tourette syndrom in the BG circuit

Answer 15

• increased dopamine from substantia nigra

- overactivity in direct pathway - disinhibition of unwanted movement

Question 16

symptoms of tourettes

Answer 16

• motor tics
• echolalia (repeating someones words)
• palilalia (repeatings ones own words)
• coprolalia (production of obcenities)

Question 17

Tourettes syndrom aberrant selection

Answer 17

• aberrant focus of activity in the striatum leads to activity in the direct pathway
• and disinhibition of undesired movement
• can be treated sometimes with dopamine antaonists