APPP 05: Gross Anatomy of the CNS – Basal Ganglia and Cerebellum Function in Motor Planning Flashcards
What are the 5 major structures of the basal ganglia?
- caudate nucleus
- putamen
- globus pallidus
- subthalamic nucleus (STN)
- substantia nigra
What is the striatum?
caudate nucleus + putamen
What is the structure of the globus pallidus (GP)?
- external segment (GPe)
- internal segment (GPi)
What is the structure of the substantia nigra (SN)?
- SNpc – contains dopaminergic neruons
- SNpr – considered a displaced piece of GPi
What are the functions of the basal ganglia? (2)
- work primarily by integrating signal from the cerebral cortex and outputting to the thalamus
- have a role in the initiation of movements, thoughts, and motivations
What are the main neurotransmitters involved with basal ganglia function? (4)
- glutamate
- acetylcholine
- dopamine
- GABA
What are the two functioning pathways of the basal ganglia?
both outflow from the striatum
- direct – movement initiation
- indirect – movement termination
Describe the direct pathway of the basal ganglia.
stimulatory – movement initiation
- GABA neurotransmitter release at GPi/SNpr inhibits GPi/SNpr activation
- no GABA release at the thalamus, resulting in increased activity of thalamus
- motor cortex
- spinal cord/brainstem
Describe the indirect pathway of the basal ganglia.
inhibitory – movement termination
- GABA release at GPe inhibits GPe neurons
- GPe does not release GABA, resulting in increased activity of STN
- STN releases glutamate and activates GPi/SNpr GABAergic neurons
- GABA is released at thalamus
- reduced excitatory input to the cortex
What is the function of the striatum?
- receives excitatory glutamatergic input from cerebral cortex
- receives dopaminergic (DA) input from SNpc
Striatum
- glutamate stimulates interneurons which use acetylcholine as a neurotransmitter on the direct and indirect pathway
- interneurons in the striatum and neurons from the SNpc connect with neurons within the striatum
- striatal neurons in the direct pathway express the excitatory D1 DA receptor and inhibitory M4 ACh receptor
- striatal neurons in the indirect pathway express the inhibitory D2 DA receptor and excitatory M1 ACh receptor
Modulation of the 2 basal ganglia paths by dopamine.
- SNpc provides dopaminergic innervation to the striatal neurons and modulates the relative activity of the two pathways
- DA released in the striatum leads to increase the activity of the direct pathway and reduce the activity of the indirect pathway
How does dopamine release at the striatum affect the direct pathway?
increases the activity of the direct pathway
- GABA neurotransmitter release inhibits GPi/SNpr activation
- no GABA release at thalamus
How does dopamine release at the striatum affect the inhibitory pathway?
reduces the activity of the indirect pathway
- less glutamate release at GPi/SNpr
- less GABA release occurs at thalamus
What can basal ganglia dysfunction cause?
involuntary muscle contractions, or difficulty in initiating muscle contraction
- Parkinson disease
- Huntington’s disease
What are the 4 characteristic signs of Parkinson disease as a result of neuron loss?
(suggests difficulty in initiation movement – not enough dopamine)
- bradykinesia – slowed movement
- rigidity – increased resistance
- tremor – rhythmic oscillatory movement around joints
- gait/balance problems
What is Parkinson disease?
characterized by a loss of dopamine neurons projecting from the SNpc to the striatum (in basal ganglia)
- 2nd most common neurodegenerative disease
- dopamine usually overrides ACh, initiates D1 neurons, and inhibits D2 neurons
Describe the direct and indirect pathways of patients with Parkinson disease.
- direct pathway – less active
- indirect pathway – increased activity
What is the treatment for Parkinson disease?
levodopa – form a dopamine that can cross the BBB
- in early PD, management can be with exercise and lifestyle
- mild symptoms – anticholinergics
- most progress and levodopa is eventually required
What is the cause of Huntington disease?
autosomal dominant inherited disorder – mutation in the Huntington gene (excessive CAG repeats)
- results in abnormal protein – neuronal damage (cell death of striatal neurons)
At what age does Huntington disease occur?
- delayed onset – around 40 years old
- but rapidly progressive and ultimately fatal (15-20 years post-diagnosis)
What is Huntington disease?
gradual onset of motor incoordination
- movement disorder – jerk-like movements that are involuntary and irregular
- progressive motor dysfunction – chorea (rapid, involuntary movements), asthetosis (slow, writhing movement), ballism (flailing movements of limbs)
- cognitive decline – loss of spatial awareness
- psychiatric disturbances – depression, anxiety
What happens to neurons in Huntington disease?
- loss of GABA neurons in striatum
- region of the striatum containing D2 neurons (indirect pathway) are affected earlier in the disease progression
- interneurons are largely unaffected
How does Huntington disease affect the direct and indirect pathways?
- neurons that project from the striatum to the GPe and form the indirect pathway are affected early in the course of the disease
- leads to loss of inhibition on the GPe, resulting in a reduced STN glutamatergic output to the GPi
What is the treatment for Huntington disease?
- tetrabenazine (inhibitors of VMAT2 transporter) – depletes dopamine and reduces the severity of chorea
- but none slow the disease progression
What is most of the information required for complex movements generated by?
basal gangli and cerebellum in coordination with the motor cortex
What information does the cerebellum receive?
information from the cerebral cortex and basal ganglia about the position of the body
Does the cerebellum initiate motor commands?
NO – but rather modifies the motor commands of the descending pathways to make movement more adaptive and accurate
- helps the limbs move smoothly and accurately by constantly adjusting muscle tone and posutre
What are vestibular nuclei?
areas in the brainstem that interact with the cerebellum
- connected with the organs of the inner ear
- enables highly coordinated movements
How many layers does the cerebellar cortex have?
3
What are the 5 types of neurons in the cerebellar cortex?
- Purkinje cell
- granular cell
- basket cell
- stellate cell
- Golgi cells
What are Purkinje cells?
- GABAergic neurons (inhibitory)
- form inhibiroy synaptic connections on neurons in the deep cerebellar nuclei
- the sole output neurons – receive two distinct excitatory inputs, namely parallel fibres and climbing fibres
What do climbing fibres do?
thought to convey error signals – mismatch between the motor command and the actual movement
Describe the main output from the cerebellum.
provides connections to a wide range of other CNS structures to control movement and influence many other functions
- excitatory input from the granule cell is integrated in the Purkinje cell with inhibitory input from the basket and stellate cells, as well as an excitatory climbing fibre input from the inferior olive
- Purkinje cell axons make inhibitory synaptic contact with neurons in the cerebellar nuclei
What is cerebellar ataxia?
lack of muscle control or coordination of voluntary movements
- persistent ataxia can be an indicator of damage to the cerebellum
