Basal Ganglia Motor System

Question 1

What are the 4 major components of the basal ganglia?

Answer 1

neostriatum

globus pallidus

substantia nigra

subthalamic nuclei

Question 2

What area of the basal primarily receives the inputs and what part sends the outputs?

Answer 2

neostriatum gets the inputs

globus pallidus sends the outputs

(substantia nigra and subthalamic nucleus are internal circuitry)

Question 3

The neostriatum consists of what two structures?

Answer 3

caudate and putamen

Question 4

What are the two type of neurons in the neostriatum?

Answer 4

1. spiny neurons - get the input and send the output
2. aspiny neurons - the interneurons

Question 5

THrough what pathway does info from the cortex reach the basal ganglia?

Answer 5

through the corticostriate pathway to the spiny neurons in the neostriatum

Question 6

Is the synapse ont he spiny neuorns excitatory or inhibitory? WHat NT?

Answer 6

excitatory - glutamate

Question 7

Are the spiny neurons inhibitory or excitatory? What NT?

Answer 7

inhibitory - GABA

Question 8

What are the two types of spiny neurons?

Answer 8

GABA/enkephalin neurons

GAMA/substance P neurons

Question 9

What are the two pathways of striatum projections and which type of spiny neurons do they use?

Answer 9

direct pathway: GABA/SP

indirect pathway: GABA/Enk

Question 10

Where do the GABA/SP spiny neurons project to in the direct pathway? (2 places)

Answer 10

mainly to the internal segment of the globus pallidus

also to the pars reticulata of the substantia nigra (SNr)

Question 11

Where does the globus pallidus send information to?

Answer 11

VA/VL thalamus, then onto motor cortex

Question 12

What is the purpose of the projections to the SNr?

Answer 12

They continue on to the thalamus and brainstem

then to the superior colliculus for eye movements

and pedunculopontin nuclei for locomotion

Question 13

Where do the GABA/Enk spiny neurons project to in the indirect pathway?

Answer 13

the external segment of the globus pallidus

Question 14

Where does the external segment of the globus pallidus project to in the indirect pathway?

Answer 14

the subthalamic nucleus (inhibitory)

Question 15

Where does the subthalamic nucleus project to in the indirect pathway?

Answer 15

the internal segment of the globus pallidus

(and the substantia nigra pars reticulata)

Question 16

Where does the vast majority of the excitatory input to the globus pallidus internus come from and what does that mean for motor control?

Answer 16

the subthalamic nuclei

since the GPi is inhibitory to the thalamus, the subthalamic nuclei therefore has most of the control over the basal ganglia output

without it, you get balismus because you lose the motor inhibition

Question 17

What role does the substantia nigra compacta play?

Answer 17

It receives inhibitory input from the GABA/SP cells

it uses dopamine to inhibit the GABA/Enk cells via D2 receptors and activate the GABA/SP cells via D1 receptors

very important for the selection of movement for reward

Question 18

Ultimately, the GPi tonically _____ the thalamus and motor funciton

Answer 18

inhibits

Question 19

Thus, to get motor activity, you need to _____ GPi activity.

Answer 19

decrease

Question 20

So…

the direct pathway _____ movement

and

the indirect pathway _____ movement

Answer 20

direct = activates movement

indirect = suppresses movement

Question 21

What is dopamine’s effect on motor activity?

Answer 21

It increases motor activity

(inhibits the indirect pathway and activates the direct pathway)

Question 22

Disruption of the basal ganglia will result in _____ movement.

Answer 22

involuntary

Question 23

Specifically, what symptoms wil result from a subthalamic lesion?

Answer 23

hyperkinetic dyskinesia = ballismus

(wild exaggerated movement of contralateral limbs)

due to loss of excitatory drive to GPi - no more inhibition on the thalamus

Question 24

What happens in Parkinson’s?

Answer 24

You have degeneration of the pigmented cells in the SNc

this means you don’t have enough dopamine

Question 25

What are the 4 major clinical findings in Parkinsons?

Answer 25

1. bradykinesia (or akinesia)
2. rigidity (not spasticity)
3. resting tremor (goes away when you do something)
4. postural instability

Question 26

What are the 4 general etiologies of Parkinson’s?

Answer 26

1. not known for most - maybe oxidative stress?
2. encephalitis lethargica (viral encephalitis)
3. toxins - CO and manganese
4. Head truma - think Muhammed Ali

Question 27

What is the treatment for Parkinson’s?

Answer 27

L-DOPA

it’s a dopamine precursor that can cross the BBB

issue is it can produce hyperkinetic movements if given too much

Question 28

What do you get with a lesion of the globus pallidus?

Answer 28

flexion dystonia/flexion posturinng (this is a hyperactivity of motor function)

this is because you’ve lost the inhibition on the thalamus from the GPi

Question 29

What do you see in putamen lesions?

Answer 29

patients become more motoric in nature and will repeat stereotyped behaviors over and over again

Question 30

What are the symptoms of a caudate lesion?

Answer 30

more complex and cognitive…

impulsivity

vulgarity

hypersexuality

increased appetite and thirst

Question 31

What is the genetic cause of Huntington’s Chorea?

Answer 31

It’s an autosomal dominant CGA repeat (gain of function) on the short arm of chromosome 4.

Question 32

When is the onset of Huntington’s?

Answer 32

25-40 years old

Question 33

What are the first neurons to die in Huntington’s?

Answer 33

the spiny neurons of the neostriatum

especially the GABA/ENK of the indirect pathway

Eventually you lose the whole striatum and cerebral cortical neurons start to die too

Question 34

What are the symptoms of Huntington’s?

Answer 34

1. involuntary movements - chorea and athetosis (wormlike movements or dancelike movements) as the indirect pathway is affected and movement isn’t suppresed
2. dementia and personality changes
3. you eventually get akinesia as the direct pathway is affected when the whole striatum dies

Question 35

What is our only real way of treating Huntington’s now?

Answer 35

give them a dopamine receptor blocker - essentially try to give them Parkinson’s disease and decrease the involuntary movement