Structure and Function of the Basal Ganglia

Question 1

What are the components of the extrapyramidal system?

Answer 1

Basal ganglia, thalamus, subthalamic nucleus, substantia nigra, red nucleus (flexors of upper limb)

Question 2

What are the functions of areas 4 and 6?

Answer 2

Area 4 - primary motor cortex - responsible for execution of movement

Area 6 - premotor / supplementary motor cortex, formulates motor program and lesions will cause akinesia (paucity of movement) / apraxia

Question 3

What is Bereitschaftspotential (BP)?

Answer 3

Readiness potential - slow negative potential on EEG seen over bilateral areas 4/6 right before a self-initiated voluntary movement occurs

-> early preparation for a motor activity

Question 4

What is the function of the basal ganglia? When are they active?

Answer 4

Optimization / filtering of motor program

• > integration of sensory and other information
• > no role in motor decisions or basic parameters of movement
• > active even during imaginary motor actions

Question 5

What is the function of the cerebellum and thalamus for movement?

Answer 5

Cerebellum - dynamic adjustment of motor execution, especially important for automatic / repetitive movements

Thalamus - relays information to and from cortex from BG, cerebellum, and sensory inputs

Question 6

What is the “pallidum”?

Answer 6

Globus pallidus internus (medial) + substantia nigra pars reticulata

(GPi/SNr)

Question 7

Give the direct pathway.

Answer 7

Striatum fires GABAnergic to inhibit Pallidum which is GABAnergic to Thalamus

Thalamus becomes disinhibited and can project glutamate to cortex, completing loop

Question 8

Give the indirect pathway.

Answer 8

Striatum fires GABAnergic to GPe which is GABAnergic to Subthalamic nucleus.

Subthalamic nucleus is disinhibited, can stimulate Pallidium which is GABAnergic to Thalamus, which inhibits cortical input by thalamus.

Question 9

How does the direct pathway make the movement filtered?

Answer 9

There is a surround inhibition of nearby motor pathways via interneurons (lateral inhibition)

Question 10

What is the “hyperdirect” connection which increases BG inhibition?

Answer 10

Cortex can direct stimulate subthalamic nucleus to reduce movement

Question 11

What is the homunculus orientation of cortical projections of sensory information to the putamen?

Answer 11

Anterior / ventral - face

Posterior / dorsal - feet

Question 12

What is the relative functional difference between the caudate and the putamen? What innervates them?

Answer 12

Putamen - motor nucleus of striatum, receives feedack from motor and sensory system to control limb movement

Caudate - dense innervation from prefrontal cortex, plays a role in planning, memory-based, and psychological aspects of motor function (motivational circuit)

Question 13

What role does the basal ganglia play in oculomotor function?

Answer 13

Caudate fires during saccadic eye movements

-> loss of caudate particularly affects eyes

Question 14

How does degeneration of striatum in Parkinson’s and Huntington’s differ and thus relate to symptoms?

Answer 14

Parkinson’s - preferential loss of putamen over caudate -> loss of motor function first

Huntington’s - preferential loss of caudate - cognitive and eye movement abnormalities. Impulsive behavior (loss of Nucleus accumbens) occurs often before choreiform movements

Question 15

What are the striosomes and what do they more contribute to? What dopamine receptors do they have?

Answer 15

Chemically distinct “islands” which receive cortical input from layers 5 and 6 in the prefrontal, insular, and temporal cortex. Mostly involved in emotional input / motivational influence of movement

Mostly have medium spiney neuronsn with D1 and D3 receptors (mostly excitatory)

Question 16

What are the matriosomes and what do they more contribute to?

Answer 16

Neuronal areas which makes up both the direct and indirect pathway - Receive cortical inputs from layer V mostly sensorimotor and association cortex. Most high concentrations of D2 receptors, but also have some D1 for the direct pathway.

Question 17

What are medium spiney neurons and what distinguishes them?

Answer 17

90-95% of striatal neurons

• GABA neurons which are distinguished by their dopamine receptor types
• > D1/D2/D3

Question 18

What do D1-expressing medium spiney neurons do?

Answer 18

They are primary striosomal, integrating sensory information, but there are also some D1-expressing medium spiney neurons which form the majority of the direct pathway.

D1 receptors are excitatory (increase cAMP)

Question 19

What do D2-expressing medium spiney neurons do?

Answer 19

They are primarily matriosomal (form the indirect motor pathway

D2 receptors are inhibitory (decrease cAMP)

Question 20

What are the functions of the large spiney neurons and the medium aspiney neurons?

Answer 20

Large spiney - cholinergic interneurons (interact directly with medium spiney)

Medium aspiney - somatostatin interneurons

Very important in the matrix, interacting with matriosomes, having a large control over motor function

Question 21

What is the function of dopaminergic input on convergence of the basal ganglia pathways?

Answer 21

Naturally, many neurons converge on a single neuron, but often pathways are kept separate (parallel)

• > controls integration of many neurons and parallel pathways in the basal ganglia
• > Removal of dopamine = convergence of pathways

Question 22

What is hemiballism?

Answer 22

Lesions in the subthalamic nucleus increase movement tendency (decreased excitation of pallidum from indirect pathway)

Question 23

What causes disruption in movement in Huntington’s disease?

Answer 23

Preferential loss of caudate = preferential loss of indirect pathway of striatum first -> increased movement

Question 24

How does Parkinson’s arise?

Answer 24

Loss of SNc

• > loss of dopamine to direct pathway (decreases movement)
• > Loss of dopamine to inhibit indirect pathway (decreases movement)

Question 25

What is the significance of loss of dopamine in parallelism vs convergence in Parkinson’s?

Answer 25

Loss of local dopamine release -> more random convergence of motor pathways (parallelism is the baseline) -> difficulty preventing firing of abnormal motor programs

-> random convergence generates the oscillations of Parkinson’s