The structure and function of the basal ganglia

Question 1

What are the basal ganglia substrates?

Answer 1

> Striatum:

• dorsal striatum = caudate nucleus + putamen
• ventral striatum = nucleus accumbens

> Globus pallidus

> Subthalamic nucleus

> Substantia nigra

Question 2

What are the 3 reentrant parallel loops?

Answer 2

1. Sensorimotor loop
2. Associative loop
3. Ventral loop

• different cortical areas are involved
• different connections among the basal ganglia are involved

Question 3

What are the input nuclei of the basal ganglia?

Answer 3

Caudate nucleus and putamen = striatum (ventral)

Question 4

What are the intrinsic nuclei of the basal ganglia?

Answer 4

• Subthalamic nucleus (STN)

- External segment of the globes pallidus (GPe)

Question 5

What are the output nuclei of the basal ganglia?

Answer 5

• Internal segment of globus pallidus (GPi)

- Substantia nigra pars reticulata (SNr)

Question 6

Which substrate of the basal ganglia is a neuromodulator?

Answer 6

Substantia nigra pars compacta (SNc)

- neuromodulatory input from SNc to striatum

Question 7

What is the connection of the basal ganglia output nuclei to the thalamus?

Answer 7

Inhibitory connection

Question 8

What is the connection of the thalamus to the cortex?

Answer 8

Excitatory connection

Question 9

What are the pathways in the basal ganglia, from the striatum to the output nuclei?

Answer 9

1. Indirect pathway: striatum -> GPe -> STN -> output nuclei (GPi + SNr) -> thalamus
2. Direct pathway: striatum -> output nuclei (GPi + SNr)

Question 10

What is the connection between the cortex and the striatum?

Answer 10

Excitatory connection

Question 11

What is the connection specificity of the parallel reentrant loops within the basal ganglia?

Answer 11

Connections of the parallel reentrant loops subserve distinct functions

Question 12

Why is the movement modulation through disinhibition?

Answer 12

Because the output nuclei (GPi ; SNr) of basal ganglia has inhibitory connections to the thalamus, which has excitatory connections to the cortex
-> output nuclei have to be inactivated so they do not inhibit the activity of the thalamus

Question 13

How is the activity of the basal ganglia output nuclei?

Answer 13

Output nuclei (GPi ; SNr):

• is inhibitory
• maintains normally a high tonic level of discharge (action potentials), suppressing the activity of the thalamus

Question 14

How does the movement modulation occur?

Answer 14

Through disinhibition of thalamocortical target regions:

• you need an impaired activity of the output nuclei (GPi ; SNr) to disinhibit the thalamus, which would cause an excitatory activity towards the cortex

Question 15

What characterises the activity of the external segment of the globus pallidus?

Answer 15

GPe:

• inhibitory to STN
• maintains normally a high tonic rate of discharge (like the output nuclei)

Question 16

How does the activation of the indirect pathway within the basal ganglia suppresses action (movement)?

Answer 16

1. Phasic cortical excitation -> excitatory discharge in the striatum
2. Activated striatum is inhibitory to GPe
3. Inhibited GPe, with its normal high tonic discharge rate, has no inhibitory action on STN
4. STN can fire excitatory activity to output nuclei (GPi ; SNr)
5. Output nuclei, with its normally high tonic discharge rate, is excited by STN -> enhanced inhibition of thalamus -> suppresses action (movement)

Question 17

How does the activation of the direct pathway within the basal ganglia promote action (movement)?

Answer 17

1. Phasic cortical excitation -> excitatory discharge in the striatum
2. Activated striatum is inhibitory to output nuclei (GPi ; SNr) -> transient inactivity of output nuclei
3. Inactivated output nuclei (inhibitory to thalamus) -> disinhibition of thalamic activity
4. Transient activity of thalamus -> promotes action (movement)

Question 18

What has recent research shown about the activity of the indirect and direct pathways of the basal ganglia?

Answer 18

They are both cooperatively active

Question 19

How is dopamine a modulator of the basal ganglia pathways?

Answer 19

DA input arises from the SNc

• D1 receptors for direct pathway
• D2 receptors for indirect pathway

Question 20

Why do the basal ganglia pathways respond differently to dopamine?

Answer 20

Because of the different nature of D1 and D2 receptors

Question 21

What is the action of D2 signalling in the basal ganglia?

Answer 21

D2 signalling suppresses firing in indirect pathway neurons

• reduction of inwards depolarising currents
• increase of hyper polarising currents

-> diminishes spiking in indirect pathway -> less activity of output nuclei (GPi ; SNr) -> reduces inhibitory effect on thalamus -> facilitates movement

Question 22

What is the action of D1 signalling in the basal ganglia?

Answer 22

D1 signalling facilitates strong cortical phasic inputs on striatum, and thus facilitates movement

• enhances Ca2+ currents
• reduces K+ currents

-> increases the spiking of neurons in striatum -> facilitates striatal signalling -> inhibits output nuclei which then doesn’t inhibit thalamus -> promotes movement

Question 23

What are optogenetics?

Answer 23

Pulse of light expresses a factor in neurons

-> allows activation of these neurons

Question 24

What did the study with ontogenetic activation of D1 and D2 in the basal ganglia show?

Answer 24

> Optogenetic D1 activation -> activates direct pathway -> facilitates movement (action)

> Optogenetic D2 activation -> activates indirect pathway -> suppresses movement (action) -> inhibits motor behaviour

=> Any problems in the activity of the direct or indirected pathways can be related to diseases/disorders
e.g. Parkinson’s, Huntington’s, Dystonia, Abulia, Dementia, Tourett’s Syndrome, ADHD, OCD, Depression, Schizophrenia

Question 25

What happens in Parkinson’s disease?

Answer 25

Specific loss of dopamine neuronal input predominantly in the substantia nigra pars compacta (SNc)

• > direct pathway becomes less active -> action selection is suppressed
• > indirect pathway becomes more active (no inhibition of GPe) -> action inhibition is facilitated

=> Loss of SNc dopamine neurons leads to tremor, rigidity, bradikynesia
BUT also non-motor symptoms (e.g. sleep disturbances)

Question 26

How is abulia/athymhormia a basal ganglia-related disorder?

Answer 26

Lesions of the globus pallidus and striatopallidal pathway
-> indirect pathway (inhibitory connection between striatum and GPe)

-> impairment of movement initiation, maintenance, and progress

Question 27

What is Kant’s view on free will?

Answer 27

“A person acts freely if he does of his own accord what must be done”

Question 28

How are people with basal ganglia dysfunction deprived of free will?

Answer 28

They are impaired in their actions

• loss of freedom of activity
• deprived in expressing their free will

Question 29

What did Sten Grillner (Karolinska Institute) say that suggests free will related to the basal ganglia functioning?

Answer 29

Sten Grillner:

“ The only output of the nervous system is the motor system, wether in cognition or action.”

Question 30

How is the arthropod central complex similar to the vertebrate basal ganglia?

Answer 30

> Inactivation of the central complex in insects alters action

> They both have spatially organised parallel-projecting loops that integrate and convey sensorimotor representations which select and maintain behavioural activity

> They both have similar genetic programs underlying their formation and function

> Similar behavioural (action selections) and pathological manifestations

> Corresponding circuit organisation
- numerous studies suggest the central complex is involved in voluntariness