The Basal Ganglia

Question 1

What is this?

Answer 1

Collection of subcortical nuclei with the forebrain

Question 2

What is this important for?

Answer 2

Movement - adjust the force of our movements

Question 3

Where does it receive input from?

Answer 3

All areas of the neocortex - motor cortex and the limbic cortex
Project back to the motor cortex
Allows us to adjust the force of our movements

Question 4

What is the volume hypothesis?

Answer 4

The internal globus pallidus acts like a volume dial and projects to the thalamus to the motor cortex

Question 5

What are the two pathways in the basil ganglia?

Answer 5

Direct - inhibitory effect of Gpi: too much activity leads to overactivity in the thalamus and amplified force of movement. When you inhibit the inhibitory, get disinhibition, more force

Indirect - excitatory effect of Gpi: too much activity leads to under activity in the thalamus and reduced force of movement. Inhibits the globes pallidus, releases more GABA, reduces outcome

Question 6

What does damage to the basal ganglia cause?

Answer 6

Hyperkinetic symptom

Hypokinetic symptom

Question 7

What is hyperkinetic symptom?

Answer 7

Symptoms of brain damage that result in excessive involuntary movements, as seen as in Huntington’s chorea or hemiballism

Question 8

What is hypokinetic symptom?

Answer 8

Symptom of brain damage that result in a paucity of movement, as seen in Parkinsons disease - won’t see movement, more rigid

Question 9

What is Huntington’s chorea?

Answer 9

Genetic disorder, affects muscle coordination

Symptoms: excessive spontaneous movements, irregularly timed, randomly distributed, and abrupt in character

Question 10

What is Huntington’s chorea caused by?

Answer 10

Atrophy of caudate nucleus and putamen (degeneration of indirect pathway neurons, direct pathway spared) - don’t get inhibition, so get random movements

Question 11

What drugs reduce Huntington’s chorea?

Answer 11

Antipsychotics - that block dopamine transmission - so reduce the amounts of movements
Anxiolytic GABAergic drugs - that increase inhibitory transmission

Question 12

What is hemiballism?

Answer 12

Caused by stroke to the sub thalamic nucleus - indirect pathway not working, so inhibitory not working, get too much movement
results in involuntary, fast, movements
Treatment - clozapine - dopamine blocker

Question 13

What is Parkinson’s disease?

Answer 13

Slowly progressive disorder than affects movement, muscle control and balance

Symptoms: slowness of movement, resting tremor, stiffness of muscles, ‘gait’: small shuffling of steps

Question 14

What is Parkinson’s disease caused by?

Answer 14

Loss of substantia nigra that sends dopamine projections to putamen that controls movement and coordination - degeneration of neurons

can be chemically induced by the toxin ‘MPTP’, thought it was heroin, woke up with Parkinson’s - use it in animals to mimic symptoms to help drugs

Question 15

How can you treat Parkinson’s?

Answer 15

L-dopa - increases dopamine

Question 16

What does dopamine increase?

Answer 16

Dopamine normally increases activity in the direct pathway (D1R expressing) neurons, and decreases activity in the indirect pathway (D2R expressing neurons)

Question 17

What does MPTP treated to monkeys show?

Answer 17

Show that there is overactivity in the indirect pathway and under activity in the direct pathway - the turning up system (direct pathway) is less active, and the turning down system (indirect pathway) is more active

Globus pallidus internal can be lesioned to treat symptoms of Pd

Question 18

How can you induce parkinsonian symptoms?

Answer 18

Following dopamine-projection lesions in striatum
Use 6-hydroxydopamine (6-OHDA) to lesion DA terminals in striatum
Use virus to express light sensitive ‘channelrhodopsin’ in only D1R-expressing neurons (direct pathway) in lesioned area
Optogenetic activation of D1R-expressing striatal neurons by shining blue light into striatum
Improvement in fine movement, decreased freezing, increased locomotor activity - activating D1, restored the symptoms