The Basal Ganglia

Question 1

What are the basal ganglia?

Answer 1

a group of nuclei of varied origin that act as a functional unit

Question 2

Where are nuclei of telencephalic origin?

Answer 2

basal to the overlying cerebral cortex

Question 3

What is the striatum?

Answer 3

a cluster of interconnected nuclei that form part of the basal ganglia involved in decision making functions

Question 4

What are the 3 nuclei of the corpus striatum?

Answer 4

• caudate nucleus
• lentiform nucleus
• nucleus accumbens

Question 5

What is the structure of the caudate nucleus?

Answer 5

C-shaped, following the curve of the lateral ventricle

Question 6

What is the lentiform nucleus made up of?

Answer 6

• internal and external globus pallidus
• putamen

Question 7

What is the input portion of the basal ganglia?

Answer 7

the caudate-putamen connections which receive projections from the overlying cerebral cortex

Question 8

Where is the subthalamic nucleus and what is its origin?

Answer 8

inferior to the thalamus of diencephalic origin

Question 9

Where is the substantia nigra and what is its origin?

Answer 9

in the midbrain of mesencephalic origin

Question 10

What does the substantia nigra consist of?

Answer 10

• substantia nigra pars compacta
• substantia nigra pars reticulata

Question 11

What neurons use dopamine as a neurotransmitter?

Answer 11

those that contain a lot of neuromelanin

Question 12

What are the 5 functional entities of the basal ganglia and what type of neurons do they have?

Answer 12

• corpus striatum (GABAergic neurons)
• GPe (GABAergic neurons)
• STN (glutamatergic neurons)
• GPi and SNr (GABAergic neurons)
• SNc (dopaminergic neurons)

Question 13

What is the major afferent projection received by the striatum?

Answer 13

glutamatergic excitatory input from the cerebral cortex

Question 14

What are the major output nuclei of the basal ganglia?

Answer 14

GPi and SNr

Question 15

What do the GPi and SNr exert their inhibitory influence on?

Answer 15

the excitatory neurons located in the ventral tier thalamic nuclei

Question 16

What are the 2 major projection systems between the input and output structures of the basal ganglia?

Answer 16

direct and indirect pathways arising from separate neuronal populations in the striatum

Question 17

Describe the direct pathway of the basal ganglia

Answer 17

• cortical inputs from motor areas excite striatal neurons that contain substance P and dynorphin
• GABAergic projections monosynaptically inhibit the GPi-SNr which decreases inhibition of the thalamus
• this allows thalamocortical circuits to become more active, facilitating the initiation of voluntary movements

Question 18

Describe the indirect pathway of the basal ganglia

Answer 18

• cortical inputs from motor areas excite striatal neurons that contain substance P and enkephalin
• GABAergic projections inhibit the GPe which decreases inhibition of the STN
• activation of the STN excites the GPi and SNr which increases inhibition of the thalamus, resulting in suppression of unwanted or inappropriate movements

Question 19

What does dopamine do at the striatal level?

Answer 19

facilitate transmission along the direct pathway but inhibit transmission along the indirect pathway

Question 20

What do dopamine receptors D1 and D2 mediate respectively?

Answer 20

• D1 = dopamine facilitating transmission along direct pathway
• D2 = dopamine inhibiting transmission along indirect pathway

Question 21

What is released from inhibition in hyperkinetic disorders?

Answer 21

SNr and GPi

Question 22

How do hyperkinetic disorders arise?

Answer 22

inhibitory output to the thalamus is increased and thalamic input to the cortex is decreased

Question 23

What causes PD?

Answer 23

degeneration of dopaminergic neurons of the SNc

Question 24

What are seen in SNc neurons?

Answer 24

Lewy bodies

Question 25

What are the main risk factors of PD?

Answer 25

• age
• genetic predisposition
• environmental causes

Question 26

What is the pathology of PD?

Answer 26

• mitochondrial damage
• free radicals
• proteasome dysfunction

Question 27

What are signs of PD?

Answer 27

• resting tremor
• rigidity and stiffness
• bradykinesia or hypokinesia
• postural inability

Question 28

What are pharmacotherapies of PD?

Answer 28

• dopamine agonists to replace lost dopamine
• levadopa
• co-administration of carbidopa
• MAO-B inhibitors that slow down dopamine breakdown

Question 29

What is levadopa?

Answer 29

dopamine precursor that crosses the blood-brain barrier

Question 30

Give an example of surgical treatment of PD

Answer 30

deep brain stimulation that inhibits STN and related thalamic nuclei

Question 31

What do drugs of abuse do?

Answer 31

increase the extracellular concentration of dopamine in the nucleus accumbens

Question 32

Where do the dopaminergic neurons of the VTA project?

Answer 32

the nucleus accumbens

Question 33

What does the ability of drugs of abuse to induce changes in dopamine concentration result in?

Answer 33

overactivation of the neuronal processes that highlight saliency

Question 34

What does addiction result from?

Answer 34

the repeated perturbation of reward circuits due to marked dopamine increases followed by dopamine decreases

Question 35

What do drug-addicted subjects show decreases in?

Answer 35

number of dopamine D2 receptors

Question 36

What does decreased dopamine sensitivity lead to?

Answer 36

decrease in interest in ordinary, day-to-day environmental stimuli