Basal Ganglia II

Question 1

What is the name for the type of neurons that recieve the information in the dorsal striatum (caudate nucleus & putamen)

Answer 1

medium spiny neurons

Question 2

The large dendritic trees of the medium spiny neurons in the dorsal stiatum integrate convergent inputs from which locations in the brain: [3]

Where do the the inputs get sent to? [2]

Answer 2

Spiny neurons inputs:
* Cerebral cortex - specifically the frontal cortex: primary motor cortex and parietal cortex: primary somatosensory cortex
* substantia nigra pars compacta (from the midbrain)
* Local circuit neurons within the corpus striatum (GABAergic)

Sent to the ouput zones:
* globus pallidus (internal AND external)
* substantia nigra pars reticula (SNr)

Question 3

Where do the following output zones of the basal ganglia send information to?

globus pallidus external (GPe) [1]
globus pallidus internal (GPi) [1]
substantia nigra, pars reticula (SNr) [1]

Answer 3

globus pallidus external (GPe): subthalamic nucleus
globus pallidus internal (GPi): ventral anterior (VA) / Ventrolateral (VL) thalamic nuclear complex
substantia nigra, pars reticula (SNr): superior colliculi

Question 4

Describe the loop from frontal & parietal cortex to the thalamus

Answer 4

Frontal and parietal cortex
to the
dorsal striatum (caudate nucleus and putamen)
to the
globus pallidus internal
to the
VA / VL thalamic nuclear complex

Question 5

Label A-E of the basal ganglia circulatory that regulates movement [5]

Answer 5

A: caudate nucleus & putamen
B: substantia nigria pars reticulata
C: globus pallidus internal
D: superior colliculus
E: VA / VL complex - in the thalamus

Question 6

Neurons from substantia nigra pars reticula (SNr) synapse onto neurons in the []

Answer 6

Neurons from substantia nigra pars reticula (SNr) synapse onto neurons in the superior colliculus (midbrain)

Question 7

State whether if the following are excitatory or inhibitory and state what NT used

• input from cortical neurons that input to the striatum [2]
• dorsal striatum AND globus pallidus neurons [2]

Answer 7

Frontal cortex input: Excitatory glutamate

• dorsal striatum and globus pallidus neurons: inhibitory GABAnergic neurons

Question 8

Describe the concept of double inhibition / disinhibition of the VA / VL complex

Answer 8

The caudate and putamen contain inhibitory GABAergic neurons that project onto

Globus pallidus internal neurones - which are also inhibitory GABAergic neurons

This creates overall excitation

Question 9

Below is a coronal section of the cerebrum. Which of the following labels corresponds to an intrinsic nuclei of the basal ganglia?

A

B

C

D

Answer 9

Below is a coronal section of the cerebrum. Which of the following labels corresponds to an intrinsic nuclei of the basal ganglia?

A

B

C

D

Question 10

Which structure separates the caudate nucleus from the putamen?

Lateral ventricle

Internal capsule

Globus pallidus

Claustrum

Answer 10

Which structure separates the caudate nucleus from the putamen?

Lateral ventricle

Internal capsule

Globus pallidus

Claustrum

Question 11

Describe, using the concept of disinhibition, when there is no activity / input from the cortical region, why no movement occurs from motor cortex

Answer 11

• No excitatory input to the striatum (caudate nucleus and putamen) from the cortical regions
• This means that the globus pallidus is tonically active and therefore inhibitory
• This inhibits the VA/VL complex of the thalamus
• Which creates no overall excitation and motor cortex is inactive

Question 12

Describe, using the concept of disinhibition, when there is activity / input from the cortical region, why movement occurs from motor cortex

Answer 12

When active / input from cortical region (excitatory glutamate neurons)
Causes the striatum to increase inhibition of the
the globus pallidus.
This will reduce inhibition to the VA/VL complex of the thalamus creates disinhibition (double double inhibition)
This leads to the excitation of motor cortex

Question 13

Describe the direct pathway of the basal ganglia

Answer 13

1. Dorsal striatum recieves dopaminergic inputs from the substantia nigra AND glutamatergic input from the association cortexes
2. The dorsal striatum releases GABA which projects onto the internal globus pallidus.
3. This Increases inhibition on the GPi
   4 The GPi then projects less inhbitory GABA onto the motor thalamus
4. This causes reduced inhibition of motor thalamus (double double inhibition)
5. Allows changes in cortical motor program

Question 14

Describe the indirect pathway of the dorsal ganglia

Answer 14

Excitation of dorsal striatum causes the release of dorsal striatum GABA (inhibitory)

This causes projects onto globus pallidus external segment: causes increased inhibition of GPe

This causes the globus pallidus external segment to release inhibitory GABA onto the subthalamic nucleus: causes reduced inhibition of STN

This causes the subthalamic nucleus to release inhibitory GABA onto the globus pallidus internal segment: which increases the activation of GPi

This causes the globus pallidus internal segment to release inhibitory GABA onto the motor thalamus: which creates increased inhibition of motor thalamus

OVERALL DEACTIVATION OF MOTOR THALAMUS -> decreased motor cortex activation.
NO GO pathway.

Question 15

Describe briefly the role of the hyperdirect pathway [1]

Answer 15

The hyperdirect pathway may play a role in preventing or quickly stopping movements initiated by the direct pathway

Question 16

Describe how the hyperdirect pathway occurs

Answer 16

Signal from the pre-supplementory motor cortex bypasses the dorsal striatum and causes the release of glutamate (excitatory) onto subthalamic nuclei

This causes activation of subthalamic nuclei, which releases glutamate onto the GPi

Activation of GPi causes release of GABA (inhibitory) to the VA VL thalamus - which stops motor cortex

Question 17

When at rest or doing a repetitive movement (e.g., talking):
the indirect pathway is []
the direct pathway is []

Answer 17

When at rest or doing a repetitive movement (e.g., talking):
the indirect pathway is active
the direct pathway is inactive

Question 18

Name the two receptors found in dorsal striatum that activated by neurons from the substantia nigra

Answer 18

substantia nigra has neurons that activate D1 or D2 receptors on dorsal striatum

Question 19

Describe the effect of the activation of the D1 dopaminergic receptors

Answer 19

The D1 dopaminergic receptor activated:

• Increases cAMP
• Increases the sensitivity of striatal GABA neurons to glutamate (makes the glutatemate MORE EXCITABLE)
• Causes more activation of the direct pathway

End result: INCREASED MOTOR ACTIVITY

Question 20

Describe the effect of the activation of the D2 dopaminergic receptors

Answer 20

The D2 dopaminergic receptor activated:

• decreases cAMP
• Decreaes the sensitivity of striatal GABA neurons to glutamate (makes the glutatemate LESS EXCITABLE)
• Causes increased inhibition of the sub-thalamic nucleus
• This means get increaed inhibition of the GPi
• This causes less inhibition of the VL / VA

End result: INCREASED MOTOR ACTIVITY

Question 21

Overall effect of dopamine modulation on basal ganglia:

What is the effect of D1 receptor on direct pathway? [1]
What is the effect of D2 receptor on indirect pathway? [1]

Answer 21

D1 receptors: INCREASES the responsiveness of the direct pathway to cortical inputs
(facilitates the direct pathway)

D2 receptors: DECREASES the responsiveness of the indirect pathway to cortical inputs
(inhibits the indirect pathway)

Question 22

Is Parkinsons disease a hyperkinetic or hypokinetic disease? [1]
Is Huntingdons disease a hyperkinetic or hypokinetic disease? [1]

Answer 22

Parkinsons: hypokinetic disease
HD: hyperkinetic disease

Question 23

Explain pathophysiology of Parkinsons disease [2]

Answer 23

-Loss of dopaminergic neurons in the substantia nigra, which project to and innervate the dorsal striatum.
- Less D1 and D2 activation
- The indirect pathway is therefore faciliated and becomes dominant

Question 24

Name the 3 classic symptoms of Parkinsons disease [3]

Answer 24

bradykinesia, tremor and rigidity.

Question 25

Name the symptoms of HD [4]

Answer 25

chorea - movement disorder that causes sudden, unintended, and uncontrollable jerky movements of the arms, legs, and facial muscles.
personality changes (e.g. irritability, apathy, depression) and intellectual impairment
dystonia
saccadic eye movements - abruptly change the point of fixation.

Question 26

Describe the initial pathophysiology of HD

Answer 26

Loss, in the dorsal striatum, of GABAergic medium spiny neurons of the D2 receptors in the indirect pathway

Direct pathway becomes dominant

(Loss of the brake - causes hyperkinetic neurons)

Question 27

Describe the late stage pathophysiology of HD

Answer 27

Both direct and indirect pathways degenerates: causes rigidity and bradykinesia becomes dominant

Question 28

Describe what ballismus and Athetosis are [2] and what they’re caused by [2]

Answer 28

Athetosis:
* slow, involuntary regular writhing movements of the fingers, hands, toes and feet (in some cases, arms, legs, neck and tongue
* Lesions to the striatum; often a result of cerebral palsy

Ballismus:
* a type of chorea, usually involving violent, involuntary flinging of one arm and/or one leg (usually one side of the body is affected: Hemiballismus). The movements are wider and more intense than chorea
* Damage to subthalamic nucleus