The structure and function of the basal ganglia Flashcards
What are the basal ganglia substrates?
> Striatum:
- dorsal striatum = caudate nucleus + putamen
- ventral striatum = nucleus accumbens
> Globus pallidus
> Subthalamic nucleus
> Substantia nigra
What are the 3 reentrant parallel loops?
- Sensorimotor loop
- Associative loop
- Ventral loop
- different cortical areas are involved
- different connections among the basal ganglia are involved
What are the input nuclei of the basal ganglia?
Caudate nucleus and putamen = striatum (ventral)
What are the intrinsic nuclei of the basal ganglia?
- Subthalamic nucleus (STN)
- External segment of the globes pallidus (GPe)
What are the output nuclei of the basal ganglia?
- Internal segment of globus pallidus (GPi)
- Substantia nigra pars reticulata (SNr)
Which substrate of the basal ganglia is a neuromodulator?
Substantia nigra pars compacta (SNc)
- neuromodulatory input from SNc to striatum
What is the connection of the basal ganglia output nuclei to the thalamus?
Inhibitory connection
What is the connection of the thalamus to the cortex?
Excitatory connection
What are the pathways in the basal ganglia, from the striatum to the output nuclei?
- Indirect pathway: striatum -> GPe -> STN -> output nuclei (GPi + SNr) -> thalamus
- Direct pathway: striatum -> output nuclei (GPi + SNr)
What is the connection between the cortex and the striatum?
Excitatory connection
What is the connection specificity of the parallel reentrant loops within the basal ganglia?
Connections of the parallel reentrant loops subserve distinct functions
Why is the movement modulation through disinhibition?
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
How is the activity of the basal ganglia output nuclei?
Output nuclei (GPi ; SNr):
- is inhibitory
- maintains normally a high tonic level of discharge (action potentials), suppressing the activity of the thalamus
How does the movement modulation occur?
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
What characterises the activity of the external segment of the globus pallidus?
GPe:
- inhibitory to STN
- maintains normally a high tonic rate of discharge (like the output nuclei)
How does the activation of the indirect pathway within the basal ganglia suppresses action (movement)?
- Phasic cortical excitation -> excitatory discharge in the striatum
- Activated striatum is inhibitory to GPe
- Inhibited GPe, with its normal high tonic discharge rate, has no inhibitory action on STN
- STN can fire excitatory activity to output nuclei (GPi ; SNr)
- Output nuclei, with its normally high tonic discharge rate, is excited by STN -> enhanced inhibition of thalamus -> suppresses action (movement)
How does the activation of the direct pathway within the basal ganglia promote action (movement)?
- Phasic cortical excitation -> excitatory discharge in the striatum
- Activated striatum is inhibitory to output nuclei (GPi ; SNr) -> transient inactivity of output nuclei
- Inactivated output nuclei (inhibitory to thalamus) -> disinhibition of thalamic activity
- Transient activity of thalamus -> promotes action (movement)
What has recent research shown about the activity of the indirect and direct pathways of the basal ganglia?
They are both cooperatively active
How is dopamine a modulator of the basal ganglia pathways?
DA input arises from the SNc
- D1 receptors for direct pathway
- D2 receptors for indirect pathway
Why do the basal ganglia pathways respond differently to dopamine?
Because of the different nature of D1 and D2 receptors
What is the action of D2 signalling in the basal ganglia?
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
What is the action of D1 signalling in the basal ganglia?
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
What are optogenetics?
Pulse of light expresses a factor in neurons
-> allows activation of these neurons
What did the study with ontogenetic activation of D1 and D2 in the basal ganglia show?
> 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
What happens in Parkinson’s disease?
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)
How is abulia/athymhormia a basal ganglia-related disorder?
Lesions of the globus pallidus and striatopallidal pathway
-> indirect pathway (inhibitory connection between striatum and GPe)
-> impairment of movement initiation, maintenance, and progress
What is Kant’s view on free will?
“A person acts freely if he does of his own accord what must be done”
How are people with basal ganglia dysfunction deprived of free will?
They are impaired in their actions
- loss of freedom of activity
- deprived in expressing their free will
What did Sten Grillner (Karolinska Institute) say that suggests free will related to the basal ganglia functioning?
Sten Grillner:
“ The only output of the nervous system is the motor system, wether in cognition or action.”
How is the arthropod central complex similar to the vertebrate basal ganglia?
> 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
