Lecture 14: Basal Ganglia Flashcards
What are the functions of the basal ganglia?
- Release appropriate movements from premotor and motor areas
- Allows a smooth motion that is planned an purposeful without extraneous movements
- Allows appropriate movement to start and stop
What are the functions of the cerebellum?
- Modulate cortical output
- Controls the maintenance of equilibrium, posture and muscle tone
- Coordinates movements (and corrects for errors in movements)
How does the cerebellum modulate cortical output?
It gets information from the cortex, forms a plan and sends a signal back to the premotor cortex
What tracts does the cerebellum coordinate conscious movements for?
Corticospinal and Corticobulbar tracts
What is the Corticopontocerebellar pathway?
The pathway that descends from the premotor or supplementary motor cortex when we want to make a conscious movement
What is the pathway that allows motor planning information to enter the cerebeelum?
The Corticopontocerebellar pathway
Which peduncle does the Corticopontocerebellar pathway enter the cerebellum?
The middle cerebellar peduncle
What tract enters the middle cerebellar peduncle?
The corticopontocerebellar pathway
What does the Corticopontocerebellar pathway descend onto?
Granule cells
Why does the Corticopontocerebellar pathway descend onto Granule cells?
Because it is a mossy fiber
Is the Corticopontocerebellar pathway a mossy or climbing fibers?
It is a mossy fiber and descends on Granule cells
What happens after the corticopontocerebellar pathway descends on Granule cells?
It activates glutamatergic signaling to activate purkinje cells
What cells do Granule cells activate with glutamate?
Purkinje cells
Where does the cerebellum project to after receiving motor planning information?
It projects to the contralateral cortex via the thalamus
Which side of the cortex does the cerebellum send and receive motor plans?
It sends and receives motor plans to and from the contralateral cortex
Which side of the cortex does the basal ganglia project to?
The ipsilateral side of the cortex
Which nucleus in the thalamus does the cerebellum and basal ganglia project to?
The VA/VL nucleus
What does the basal ganglia allow for?
It allows for movements to be initiated and helps to plan for the best movement by tweaking movements in real time
If there is a lesion to the cerebellum, where would the effect be seen?
On the ipsilateral side because the corticospinal tract crosses over
What are the two different pathways of the basal ganglia?
- Indirect pathway
- Direct pathway
What nucleus in the the thalamus do both basal ganglia pathways act on?
The VA/VL nucleus
Where does the basal ganglia receive input from?
The premotor cortex (premotor cortex also acts on the cerebellum)
What will the direct or indirect pathway of the basal ganglia do?
They will either inhibit the thalamus and decrease movement or not inhibit the thalamus and promote movement
What can Cerebellar lesions cause?
- Cerebellar ataxia
- Forced Tremor
- Inability to coordinate smooth purposeful movement
What lesion would cause:
- Cerebellar ataxia
- Forced Tremor
- Inability to coordinate smooth purposeful movement
A cerebellar lesion
What is Cerebellar ataxia?
The lack of coordination of muscle movements
What is a forced tremor?
When there is no tremor at rest but there is a tremor when performing movements
What are some smooth purposeful movements that are difficult with a cerebellar lesions?
- Repetitive movement
- Finger to nose test (overshoot)
- Heel to shin test (can’t move smoothly)
What diseases can lesions to the Basal Ganglia cause?
- Parkinson’s disease (PD)
- Huntington’s disease (HD)
What parts of the brain are Parkinson’s and Huntington’s disease associated with?
The basal ganglia
What are the symptoms fo Parkinson’s disease?
- Bradykinesia (slowness of movements)
- Fine tremor at rest
- Pill rolling tremor
- Poverty of movement
How do people with Parkinson’s tend to walk?
They tend to lean forward to initiate walking because they are unable to do this due to damaged basal ganglia
What are the symptoms of Huntington’s Disease?
- Involuntary flinging and flailing of movements (chorea)
- Too much movement
What does the Postmortem brain of Huntington’s disease patients look like?
Lesions in basal ganglia (cell death and degeneration)
What does the Postmortem brain of Parkinson’s disease patients look like?
A decreased size of the substantia nigra
What does the Basal Ganglia have a major role in?
The control of normal voluntary movement
Where does the basal ganglia receive constant input from?
The cerebral cortex, muscle spindles and joints about the location and posture of the body
Where does the basal ganglia send outputs to?
The prefrontal, premotor and primary motor cortices via the thalamus
What causes Huntington’s disease?
Cell death in the caudate nucleus of the basal ganglia
What does the caudate nucleus extend into?
The lateral ventricles
What projections are in the internal capsule?
Thalamocortical and corticothalamic projections
What is found in the genus of the corpus callosum?
The Corticobulbar tracts for movements of the face
Where in the brain are the corticobulbar tracts for movement of the face found?
The genu of the corpus callosum
What is in the posterior limb of the internal capsule?
The corticospinal tracts from the upper and lower part of the body
Where in the internal capsule are the corticospinal tracts for the upper and lower part of the body?
The Posterior Limb of the internal capsule
What is included in the Lentiform nucleus?
The Putamen and the internal and external Globus Pallidus
What is the substantia nigra a part of?
The basal ganglia
What is included in the striatum?
The caudate nucleus and the putamen
What are the caudate nucleus and the putamen collectively known as?
The Striatum
What are the four principal nucleus of the basal ganglia?
- Striatum (caudate + putamen)
- Globus pallidus internal and external)
- Substantia nigra (reticulata + compacta)
- Subthalamic nucleus
What are the parts of the substantia nigra?
Substantia Nigra Reticulata
Substantia Nigra Compacta
What are the parts of the Globus Pallidus?
- Globus Pallidus external
- Globus Pallidus internal
What can the basal ganglia principal nuclei be divided into?
- Input
- Output
- Intrinsic nuclei
What is the Input nucleus?
The Striatum (Caudate + Putamen)
What information does the Striatum receive?
Receives information from the cortex on the body’s position (sensory) and the motor plan from the supplementary/premotor motor cortex
Where in the basal ganglia is information from the cortex on the body’s position and the motor plan sent to?
The striatum (caudate + putamen)
What are the Output Nuclei?
Globus Pallidus and Substantia Nigra Pars Reticulata
What do the output nuclei of the Basal ganglia do?
Send out information from the basal ganglia to the supplementary motor cortex/premotor cortex to initiate or stop movements
What part of the basal ganglia Send out information from the basal ganglia to the supplementary motor cortex/premotor cortex to initiate or stop movements?
The Output Nuclei: Globus Pallidus and Substantia Nigra (Pars Reticulata)
What does the Substantia Nigra secrete?
Dopamine
Why is the Globus Pallidus the main output nuclei?
Because the Substantia nigra actually secretes dopamine to act on the striatum and not the cortex
What sits deep to the putamen?
The Globus Pallidus, the internal capsule and the thalamus
What sits underneath the thalamus?
The Subthalamic Nucleus
What is the first step of the basal ganglia when initiating a movement?
The cerebral cortex sends signals to the input nucleus of the basal ganglia using glutamate
What signals does the input nuclei of the basal ganglia receive from the cortex?
Glutamate signals
What neurotransmitter does the basal ganglia receive from the cortex?
Glutamate
After receiving excitatory information from the cortex, what does the basal ganglia do?
It communicates with itself and the Globus Pallidus Internus will release GABAergic signal to the thalamus
What must happen to the thalamus in regards to the Basal Ganglia to allow a movement?
The inhibition of the thalamus by the basal ganglia releasing GABA must be stopped
What does the thalamus release onto the cortex to allow movement to occur?
Glutamate
What part of the Basal ganglia releases GABA onto the thalamus to inhibit movement?
The Globus Pallidus Internus
What does the Globus Pallidus Internus do?
Releases GABA onto the thalamus to inhibit movement
What is the major neurotransmitter for the basal ganglia?
GABA
What are the main neurotransmitters of the basal ganglia?
GABA
Dopamine
Acetylcholine
What is the output of the basal ganglia (inhibitory/excitatory)?
The output of the basal ganglia is inhibitory because it releases GABA
What neurons in the basal ganglia contain dopamine?
The Substantia Nigra
What neurotransmitter does the substantia nigra pars compacta contain?
Dopamine
What neurons in the basal ganglia contain acetylcholine?
Intrastriatal neurons
What neurotransmitter do intrastriatal basal ganglia neurons contain?
Acetylcholine
Where does the tail of the caudate nucleus end?
At the amygdala
What sits deep to the putamen?
The Globus Pallidus
What is the Corona radiata?
Axon tracts that descend down the to the internal capsule to the basal ganglia
What does the direct pathway allow for?
It allows the basal ganglia to facilitate purposeful movements
What does the indirect pathway allow for?
It allows the basal ganglia to inhibit unwanted movement
Overall in the movement pathway, how does the basal ganglia work?
When a movement is wanted, it activates a collection of axons through the basal ganglia that eventually allow the thalamus to activate the premotor cortex onto the UMN to allow only certain muscles to contract and the rest to stay inhibited
What inhibits muscles not needed in a movement?
The indirect pathway
What is the difference between the direct and indirect pathway?
The direct pathway facilitates purposeful movements. The indirect pathway inhibits unwanted movements
What is the input nucleus of the basal ganglia?
The Striatum
Why is the striatum of the basal ganglia important?
It is the input nucleus of the basal ganglia
What neurotransmitter does input from the cortex release onto the basal ganglia?
Glutamate
What inputs does the striatum of the basal ganglia receive?
- Input from all areas of the cortex (glutamatergic(
- Excitatory inputs from the intralaminar nuclei of thalamus
- Input from the midbrain (substantia nigra pars compacta - dopamine)
Describe the input from the midbrain on the striatum?
The Substantia nigra pars compacta releases dopamine onto the striatum
What neurotransmitter does the substantia nigra pars compacta release onto the striatum?
Dopamine
What releases dopamine onto the striatum?
The Substantia nigra pars compacta
What releases glutamate and dopamine onto the striatum?
Dopamine - Substantia nigra pars compacta
Cortex - glutamate
What does the striatum project to output nuclei via?
Via indirect and direct pathway
What does activation of the direct pathway do?
Activates the direct pathway which disinhibits the thalamus leading to increase thalamocortical activity and increased movement
What does activation of the indirect pathway do?
Further inhibits thalamocortical neurons causing decreased cortical activity leading to decreased movement
What is the excitatory intrinsic connection of the basal ganglia?
The subthalamopallidal projection
What is the subthalamopallidal projection?
The only intrinsic excitatory projection of the basal ganglia - all others are GABAergic and inhibitory
Where does dopamine from the substantia nigra project to?
The striatum
What does dopamine from the substantia nigra do differently to the pathways?
It excites the direct pathway and inhibits the indirect pathway
What excites the direct pathway?
Dopamine from the substantia nigra
What inhibits the indirect pathway?
Dopamine from the substantia nigra
How does dopamine from the substantia nigra excite the direct pathway from the striatum while also inhibiting the indirect pathway from the striatum?
It acts on different receptors in the striatum
What happens once both dopamine from the substantia nigra and glutamate from the cortex is released onto the striatum?
Striatal neurons (putamen + caudate) which release GABA which inhibits the GPi from releasing GABA onto the thalamus and disinhibit it
What basal ganglia nuclei do not release GABA?
The substantia nigra (dopamine) and subthalamic nuclei (glutamate)
What does the Globus Pallidus Internus receive from the striatum?
Inhibitory and excitatory signals from different nuclei which it summates
What does the Globus Pallidus internus release and onto what?
It released GABA onto the thalamus
What happens when the direct pathway releases GABA onto the Globus Pallidus Internus?
It inhibits the Globus Pallidus Internus from releasing GABA onto the thalamus thus allowing movement
What inhibits the Globus Pallidus Internus from releasing GABA onto the thalamus?
GABA from the direct pathway of the striatum inhibit the GPi
What does the Globus Pallidus internus usually release GABA onto when no movement is wanted?
The thalamus
Overall describe how movements occur with the basal ganglai?
- Glutamate from the cortex is released on the striatum
- Dopamine from the substantia nigra is also released on the striatum
- This activates the direct pathway to release GABA onto the Globus Pallidus Internus
- This prevents the Globus Pallidus Internus from releasing GABA onto the thalamus to inhibit movement
- Thus movement is allowed
How does dopamine act in the brain?
Dopamine acts on the striatum by activating the direct pathway which disinhibits the thalamus allowing for increased movements
How does dopamine released by the substantia nigra affect the indirect pathway?
It inhibits the indirect pathway
What inhibits the indirect pathway?
Dopamine released from the substantia nigra
What happens when dopamine inhibits the indirect pathway?
It inhibits the striatum from releasing GABA onto the Globus Pallidus externus so the globus pallidus externus can go on to release GABA onto the GPi and subthalamic nuclei
What inhibits the Globus Pallidus Externus?
When a movement is wanted dopamine inhibits the indirect pathway from releasing GABA onto the Globus Pallidus Externus
What does the decreased release of GABA from striatal neurons on the Globus Pallidus externus do?
It allows the Globus Pallidus Externus to release GABA onto the Globus Pallidus Internus and onto the subthalamic nuclei
What occurs in the direct pathway when initiating a movement?
- Glutamate is released onto the stritaum from the cortex
- At the same time, dopamine is released onto the striatum from the substantia nigra pars compacta
- This activates the direct pathway causing the striatum to release GABA onto th Globus Pallidus Internus
- This GABA released onto the Globus Pallidus Internus inhibits the Globus Pallidus internus from releasing GABA onto the thalamus, allowing for movement
What occurs in the indirect pathway when initiating movement?
- Glutamate from the cortex is released onto the striatum
- Dopamine from the substantia nigra is also released onto the striatum
- The dopamine inhibits the direct pathway from releasing GABA on to the Globus Pallidus Externus
- Because GABA is no longer being released onto the Globus Pallidus Externus, the GPe releases GABA onto the GPi and the Subthalamic Nucleus
- The GABA released on the GPi prevents it from releasing GABA onto the thalamus
- The GABA released onto the subthalamic nuclei inhibits it from releasing glutamate onto the GPi so it doesn’t excite the GPi to release GABA onto the thalamus
What does inhibition of the indirect pathway by dopamine do?
Because the indirect pathway is no longer activated, it stops releasing GABA onto the Globus Palliduus Externus. The Globus Pallidus is activates and can release GABA onto the GPi and the subthalamic nucleus
What does the Globus Pallidus externus releasing GABA onto the GPi do when the indirect pathway is inhibited
The Globus Pallidus Externus releases GABA onto the GPi inhibiting the GPi from releasing GABA onto the thalamus allowing for movement
What are the steps when the indirect pathway is activated?
When the indirect pathway is activated the striatum releases GABA onto the GPe. This prevents the GPe from releasing GABA onto the GPi and the subthalamic nucleus. Causing GABA from the GPe to be released onto the thalamus
How does the Globus Pallidus Externus affect the Subthalamic Nuclei when the indirect pathway is activated?
It releases GABA onto the subthalamic nuclei, which inhibits the subthalamic nucleu from releasing glutamate onto the GPi activating it to release GABA onto the thalamus
When movement is not wanted and the indirect pathway is active what are the actions of the striatum on the GPe?
It releases GABA onto the GPe inhibiting it from releases GABA onto the GPi and the Subthalamic nucleus. This allows the GPi to release GABA onto the thalamus and allows the Subthalamic nucleus to release glutamate into the GPi further activating it to release GABA onto the thalamus
What does not having dopamine in the basal ganglia do in stopping movement?
No dopamine activates the indirect pathway which further inhibits thalamocortical neurons which decreases movement
What are the steps in stopping a movement?
- Signals from the cortex signal to stop movement
- This stop release of dopamine from the substantia nigra pars compacta
- This disinhibits the indirect pathway (activates the indirect pathway)
- Causing the striatum to release GABA onto the globus pallidus externus
- This inhibits the globus pallidus externus from releasing GABA onto the GPi and the Subthalamic nucleus
What activates the indirect pathway?
The stopping of release of dopamine from the substantia nigra pars compacta
What happens when GABA is released onto the subthalamic nucleus?
It prevents it from releasing glutamate onto the GPi
Which receptors does dopamine act on in the striatum and what do they do?
- Dopamine on D1 receptors of the striatum activate the direct pathway
- Dopamine on D2 receptors inhibits the indirect pathway
What causes Parkinson’s disease?
A deficiency in dopamine
What does the deficiency in dopamine seen in Parkinson’s do in basal ganglia?
The direct pathway is no longer able to activate and the indirect pathway is further inhibited
What does the inactivation of the direct pathway and the activation of the indirect pathway do in Parkinsons?
The Globus Pallidus externus is further inhibited by the striatum (direct pathway) resulting in decreased outflow to the subthalamic nucleus. Allowing the subthalamic nucleus to release glutamate onto the GPi which releases GABA onto the thalamus
How are the two pathways of the basal ganglia affected in parkinson’s disease?
The indirect pathway is activated and the direct pathway in inhbited
What causes Huntington’s Chorea?
The loss of striatal neurons of the indirect pathway
What disease does the loss of striatal neurons of the indirect pathway cause?
Huntington’s Chorea
What is the result of the loss of striatal neurons of the indirect pathway in Huntington’s chorea?
There is reduced striatal inhibitions of the Globus Pallidus Externus resulting in greater GABA released by the GPe to the subthalamic nucleus. This diminishes the excitatory output of the STN to the GPi resulting in reduced outflow of GABA from the GPi so it no longer inhibits the thalamus causing activation of the cortex
Where does cell death occur in Huntington’s disease?
In the caudate
What are the three types of motor disturbances caused by lesions to the basal ganglia?
- Tremor + other involuntary movements (dyskinesias/choreas)
- Changes in muscles tone + posture (increase or decrease)
- Poverty of movement (without paralysis)
What is Hemiballismus (hyperkinetic) and what causes it?
An extreme type of huntingtons usually occurs due to a stroke of the subthalamic nucleus
What does a stroke to the subthalamic nucleus as seen in hemiballismus do?
Normally, the subthalamic nucleus releases glutamate onto the globus pallidus internus to activate it to release GABA onto the thalamus. Without the subthalamic nucleus, the Globus Pallidus internus cannot be activated to release GABA onto the thalamus to inhibit movement
What are the main functions of the basal ganglia?
- Facilitate some movements and suppress others
- Compare commands for movement from motor cortices with proprioceptive feedback from evolving movement to monitor its consequences
- Maintain a finely tuned balance between the three neurotransmitter systems used by the circuitry of the BG
What are the three neurotransmitter systems used by the circuitry of the basal ganglia?
- Nigrostriatal dopaminergic system
- Nigrostriatal cholinergic (acetylcholine) system
- Striato-pallidal GABAergic system
How is the Basal Ganglia associated with the frontal lobe?
The basal ganglia have a role in cognition, mood and non-motor behaviour due to their extensive connection with the frontal lobe and limbic areas
Where do lesions in the basal ganglia show their effects?
In the contralateral body
