1,59 Basal Ganglia

Question 1

What are the 5 parts of the basal ganglia?

Answer 1

Caudate nucleus 
Putamen 
Globus pallidus 
Subthalamic nucleus 
Substantia nigra

Question 2

What sends projections in the basal ganglia?

Answer 2

The cortical areas involved in planning and execution of movement

Question 3

Where does the basal ganglia send projections to?

Answer 3

Motor relay areas of the thalamus
Ventral anterior
Ventral lateral

Question 4

Where does the thalamus send projections to?

Answer 4

Cortical areas in planning and execution

Question 5

Is the thalamus excitatory or inhibitory of the cortex?

Answer 5

Excitatory - encourgaes cortex to send messages down

Question 6

Do the basal ganglia act ipsilaterally or bilaterally?

Answer 6

Ipsilaterally

Question 7

Are there descending outputs from the basal ganglia?

Answer 7

No descending outputs

Question 8

What does a lesion in the basal ganglia result in?

Answer 8

Produces unwanted movements - because it acts inhibitory

Question 9

Explain the putamen circuit….

Answer 9

Prefrontal, premotor and somatosensory cortex
Putamen
Globus pallidus internal and external
Substantia nigra or subthalamic nucleus
Ventroanterior or Ventrolateral nuclei of the thalamus
Primary motor cortex or sma

Question 10

What is the function of the putamen circuit?

Answer 10

Subconscious execution of learned patterns of movement

Writing, cutting with scissors and hammering nails etc…

Question 11

Explain the caudate circuit…

Answer 11

Prefrontal, Premotor, Somatosensory areas
Caudate
Putamen or globus pallidus
ventral anterior or lateral nuclei of thalamus
Prefrontal area

Question 12

What is the function of the caudate circuit?

Answer 12

Cognitive planning of moving

Question 13

What would happen if there was a lesion in the caudate circuit?

Answer 13

Lesion can cause an inability to plan and initiate a movement

Question 14

What are D1 (receptor) cells?

Answer 14

Located in striatum
Excited by dopamine from the substantial nigra
excited by glutamergic projections from the cortex

Question 15

What happens when D1 cells are excited?

Answer 15

Increases inhibition of Globus Pallidus internal
Releases tonic inhibition of thalamus (less inhibition) - VA/VL
Excitation of Cortex

Question 16

What makes up the striatum?

Answer 16

Caudate and Putamen

Question 17

What is the function of the direct pathway?

Answer 17

Increases motor activity

Question 18

What is the function of the indirect pathway?

Answer 18

Decreases motor activity - inhibits unwanted movement

Question 19

What are D2 (receptor) cells?

Answer 19

Located in the striatum
Excited by cortical input
Inhibited by dopamine

Question 20

What happens when D2 receptors are excited?

Answer 20

Increases inhibition of globus palidus external
Decreases inhibition of subthalamic nucleus
Increases excitation of globus pallidus internal
Increases inhibition of the thalamus
Reduces thalamic excitation of the cortex

Question 21

Which neurotransmitters stimulate and inhibit?

Answer 21

GLUT - stimulates

GABA - inhibits

Question 22

What do the cholinergic neurones in the striatum do?

Answer 22

Opposite to dopamine
Inhibit the direct pathway
Excite indirect pathway
Net - decreased motor activity

Question 23

What happens if the cholinergic neurones in the striatum are lost?

Answer 23

Increased motor activity - Huntington’s disease

Question 24

Explain hypokinetical disorders?

Answer 24

• insufficient direct pathway output
• excess indirect pathway output
Loss of dopamine

Question 25

Explain hyperkinetical disorders?

Answer 25

• excess direct pathway output

insufficient indirect pathway output

Question 26

What is the pathophysiology of Parkinson’s?

Answer 26

Loss of nigrostriatal DA projections

Question 27

What are the symptoms of Parkinson’s?

Answer 27

Tremor at rest - pill rolling 
(no tremor - everything's gone)
Bradykinesia 
Rigidity 
Impairment of postural reflexes

Question 28

What happens to the direct and indirect pathways in Parkinson’s?

Answer 28

Indirect pathway - normally inhibited by D2 is released

Direct pathway - normal excited by D1 is diminished

Question 29

What is L-DOPA?

Answer 29

Dopamine precursor
Main treatment
This is initially effective, but after 5-10 years, 50% of patients develop DOPA-induced dyskinesia.

Question 30

What other treatment is available for Parkinson’s?

Answer 30

Deep brain stimulation
The activity of the subthalamic nucleus (STN) is increased in Parkinson’s.
Bilateral STN stimulating electrodes: high frequency stimulation inactivates the STN.

Question 31

What causes hyperkinetic disorders?

Answer 31

Caused by lesions to caudate /putamen / globus pallidus; Chorea (twitches) ; Athetosis (changeable or writhing movements); Dystonia (torsion spasm).

Question 32

What is the pathophysiology of Huntington’s disease?

Answer 32

• Atrophy of striatum (caudate + putamen)
• Loss of striatal GABAergic neurons reducing inhibition of thalamus leading to increased cortical excitation
• Neuropathological sequence
1st: loss of striatal GABA/enkephalin/D2-R neurons (indirect pathway)
2nd: loss of striatal GABA/dynorphin/D1-R neurons (direct pathway) & cortical atrophy

Question 33

What are the symptoms of Huntington’s disease?

Answer 33

Chorea (brief, involuntary movements)
dystonia (abnormal postures)
Executive function (complex tasks)
Recent and remote memory (poor retrieval) 
Depression
Psychosis
Immobility
Weight loss
Death within 10-25 years (often from pneumonia)

Question 34

What is the hutington mutation?

Answer 34

Autosomal dominant (50% chance of inheritance if one parent affected)
Defect in Huntingtin protein (function unclear) but may be involved in intracellular trafficking