Basal Ganglia

Question 1

What are the ‘basal ganglia’?

Answer 1

A set of neural structures buried deep within the cerebral hemispheres

Question 2

What structures make up the basal ganglia?

Answer 2

Caudate nucleus, putamen, globus palidus (internal and external), substantial nigra (reticulate and pars compacta) and sub thalamic nucleus

Question 3

Which structures make up the dorsal striatum?

Answer 3

Caudate nucleus and putamen

Question 4

Which structures make up the ventral striatum?

Answer 4

The nucleus accumbens

Question 5

Which structures make up the corpus striatum?

Answer 5

Globus pallidus, putamen and caudate nucleus

Question 6

Which structure of the basal ganglia forms the lateral wall of the lateral ventricles in the brain?

Answer 6

The caudate nucleus

Question 7

What is the function of the basal ganglia?

Answer 7

To process incoming information from the sensory and associated cortex and send the response from the thalamus to the supplementary motor cortex;

> Regulates intensity of stereotyped movement
Inhibits antagonistic movement
Regulates attention and cognition
Switch motor programmes

Question 8

What are ‘medium spiny neurones’?

Answer 8

The neurones present in the striatum and in the basal ganglia generally; a form of GABAergic neurone that can be influenced by the action of dopamine on D1 and D2 receptors

Question 9

By what two pathways is the striatum connected with the globus pallidus and substantia nigra?

Answer 9

The direct and indirect pathways

Question 10

Describe the direct pathway which connects the striatum with the globes pallidus and substantia nigra

Answer 10

> Medium spiny neurones in the striatum are activated by glutamatergic neurones synapsing from the cortex
The medium spiny neurones then project from the striatum to the INTERNAL globus pallidus and release GABA
This prevents the firing of medium spiny neurones from the globus pallidus interna to the thalamus; this means that glutamatergic neurones from the thalamus to the supplementary motor cortex aren’t inhibited and therefore communication can occur (disinhibition)

Question 11

What is the normal function of the direct pathway in the basal ganglia?

Answer 11

To allow changes in motor programmes e.g. to stop running or sitting down

Question 12

What is the normal function of the indirect pathway in the basal ganglia?

Answer 12

Disallows changes in motor programmes as it decreases excitatory thalamocortical projections

Question 13

Describe the indirect pathway which connects the striatum with the globes pallidus and substantia nigra

Answer 13

> Glutamatergic neurones from the cortex synapse in the striatum and activate the medium spiny neurones
The medium spiny neurones project from the striatum to the globus pallidus externa
GABAergic neurones from the globus pallidus externa travelling to the sbthalamic nucleus therefore don’t fire
The glutamatergic neurones from the sub thalamic nucleus then project to the globus pallidus interna
This stimulates the GABAergic neurones from the globus pallidus interna to project to the thalamus
There is inhibition of the glutamatergic neurones from the thalamus to the cortex which prevents changes in motor programmes

Question 14

Outline the role of dopamine in the nigrostriatal pathway

Answer 14

Facilitates the activity of the medium spiny neurones of the DIRECT pathway but INHIBIT INDIRECT pathway –> dopamine allows motor programmes to change

Question 15

Outline the function of the dopamine receptors in the nigrostriatal pathway

Answer 15

Dopamine is released from the substantia

Question 16

Which structure secretes dopamine in the basal ganglia?

Answer 16

Substantia nigra pars compacta

D1 receptors - binding of dopamine increases cAMP levels, increases sensitivity of striata cells to glutamate, facilitates the direct pathway

D2 - decreases the action of the indirect pathway

Question 17

Which pathways of the basal ganglia are active at rest?

Answer 17

Direct pathway is inactive

Indirect pathway is active

Question 18

Which pathways of the basal ganglia are active during change of movement?

Answer 18

Direct pathway is active

Indirect pathway is less active

Question 19

What two conditions are associated with dysfunction of the basal ganglia?

Answer 19

Parkinson’s and Huntington’s disease

Question 20

What is the cause of Parkinson’s disease?

Answer 20

Loss of the substantia nigra pars compacta cells, leading to loss of dopamine input to the striatum (caudate nucleus and putamen)

Question 21

What are the signs of Parkinson’s disease?

Answer 21

Don’t present until >80% of SN cells have degenerated.

> Tremor at rest
Rigidity
Bradykinesia
Loss of postural reflexes

Question 22

What is the genetic cause of Huntington’s disease?

Answer 22

Autosomal dominant mutation in the Huntington gene

Question 23

What are the symptoms of Huntington’s disease?

Answer 23

> Hyperkinesis
Ballismus (involuntary, sudden and jerky movements)
Athetosis (involuntary, smooth movements)
Dementia

Question 24

What is ballismus?

Answer 24

Involuntary, sudden and jerky movements associated with Huntington’s disease

Question 25

What is athetosis?

Answer 25

Involuntary, smooth ‘sinuous’ movements associated with Huntington’s disease

Question 26

What is the pathophysiology behind Huntington’s disease?

Answer 26

Loss of GABAergic neurones in the striatum (caudate nucleus and putamen).

• Can be seen on MRI as enlargement of the ventricles and shrinkage of the basal ganglia

Question 27

How may Huntington’s disease be treated?

Answer 27

Dopamine antagonists or atypical antipsychotics

Question 28

How may Parkinson’s disease be treated?

Answer 28

Early = levodopa, dopamine agonists, MAO-B inhibitors, COMT inhibitors

Advanced = deep brain stimulation of the subthalamic nucleus