21.4 and 21.5. Basal Ganglia and Cerebellum (HT) Flashcards
Summarise the organisation of the sensory-motor pathway.
- Sensory systems and the limbic/reticular system are responsible for our motivation to make movement, both due to sensory input and due to our emotions
- The basal ganglia and pre-motor cortical areas are involved in planning of movement
- The motor cortex programs this movement
- The cerebellum and brainstem are involved in integration
- The spinal cords and muscles execute the movement
What are the basal ganglia and where are they found?
- A group of subcortical nuclei in the brain.
- They are found at the base of the forebrain and top of the midbrain (i.e. they are subcortical).
Draw diagrams to show the subcortical loops that the basal ganglia and cerebellum are involved in.
Describe simply the subcortical loops that basal ganglia form.
- Receive information from various cortical areas
- They then process this information and pass it back to the cortex via the thalamus (ventral anterior and vental lateral nuclei)
The basal ganglia are ………, ………. structures.
- Extrapyramidal (meaning that they do not pass through the pyramids of the medulla)
- Subcortical
Summarise simply the function of the basal ganglia.
- They are involved in selection of internally-generated goal-driven movements.
- This is done because they receive information from the cortical areas and then output back to the pre-motor cortical areas via the thalamus
(In other words, the basal ganglia select motor activity that is not reflex, although it may be almost automatic due to learning)
Describe in depth the functions of the basal ganglia.
- Solve the problem of multiple competing inputs from the limbic/reticular system and cortical areas:
- There are multiple sensory, motivational and emotional inputs, as well as short and long-term goals, to the basal ganglia
- They must weight up these needs and put them in context, in order to decide which motor program is appropriate for the circumstances
- This is done by:
- Selecting the goal to respond to (e.g. quenching thirst)
- Selecting actions that will achieve that goal (e.g. movement)
- Select the exact movements required with regards to important sensory stimuli (e.g. how to move to get the water)
- Learn the outcome of actions (Outocome-Action) and the sensory cues that are associated with those outcomes (Stimulus-Outcome)
- This allows adaptation, so that efficient responses can be managed in the future
- This is called reinforcement learning
- Establish habits (Stimulus-Response)
Draw the general appearance of the basal ganglia in 3D.
What are the different basal ganglia you need to know about?
[IMPORTANT]
- Striatum
- Caudate
- Putamen
- Globus pallidus
- Internal segment
- External segment
- Subthalamic nucleus
- Substantia nigra
- Pars compacta
- Pars reticulata
Label this.
What is number 1?
Thalamus (Ventral anterior and ventral lateral nuclei)
What is number 2?
Caudate nucleus (part of striatum)
What is number 3?
Putamen (part of striatum)
What is number 4?
Globus pallidus (internal and external segments)
What is number 5?
Subthalamic nuclei
What is number 6?
Substantia nigra pars compacta
What is number 7?
Substantia nigra pars reticulata
Label this.
Label this.
Draw a diagram to show the relative 3D positions of all of the basal ganglia.
Draw and describe the subcortical loops that the basal ganglia are involved in.
[IMPORTANT]
- The blue box shows all of the basal ganglia
- The striatum receives input from the cortex
- It then outputs to the substantia nigra pars reticulata and internal globus pallidus (which are considered together), as well as the external globus pallidus
- The external globus pallidus and subthalamic nucleus are interconnected, and the subthalamic nucleus also outputs to the substantia nigra pars reticulata and internal globus pallidus
- Output from the basal ganglia is from the substantia nigra pars reticuluta and internal globus pallidus, to the thalamus and brainstem nuclei
- The substantia nigra compacta also outputs back to the striatum
- The thalamus outputs to the cortex and striatum, completing the loop
Which part of the basal ganglia is most input from the cortex and thalamus from?
Striatum
Which part of the basal ganglia is most output from the basal ganglia from and to?
- From the substantia nigra pars reticulata and internal globus pallidus.
- To the thalamus and to the brainstem nuclei.
Which two parts of the basal ganglia are frequently considered together and why?
- Substantia nigra para reticulata and internal globus pallidus
- This is because they contain similar neurons and have similar inputs/outputs
What neurons in the striatum receive input from the cortex?
Medium spiny neurons (a.k.a. spiny projection neurons)
What do medium spiny neurons in the striatum fire in response to?
- They fire in relation to cues for movement or intended movement, not movement itself.
- This is consistent with the idea that the basal ganglia are responsible for selection of motor programs.
What are the principle neurotransmitters involved in the basal ganglia that you need to know? Where is each used?
[IMPORTANT]
- Glutamate (excitatory)
- From cortex to striatum
- From subthalamic nucleus to internal globus pallidus (and internal globus pallidus + substantia nigra pars reticulata, although not mentioned)
- From thalamus to cortex and striatum (not in spec)
- GABA (inhibitory)
- From striatum, external globus pallidus and internal globus pallidus (+ substantia nigra pars reticulata)
- Dopamine (excitatory or inhibitory)
- From substantia nigra pars compacta to striatum
What are the two types of medium spiny neurons in the striatum?
[IMPORTANT]
- D1
- Enriched in D1 dopamine receptors
- Make substance P and dynorphin opioid
- D2
- Enriched in D2 dopamine receptors
- Have A2A receptors
- Make enkephalin opioid
This is because they also receive dopaminergic input from the substantia nigra pars compact (aside from the glutamatergic input from the cortex).
What neurotransmitters act on the striatum?
[IMPORTANT]
- Glutamate from the cortex
- Dopamine from the substantia nigra pars compacta
What neurotransmitters does the striatum (medium spiny neurons) use?
[IMPORTANT]
GABA
Summarise where glutamate is used in the basal ganglia system.
[IMPORTANT]
- From cortex to striatum
- From subthalamic nucleus to internal globus pallidus (and internal globus pallidus + substantia nigra pars reticulata, not in spec)
- From thalamus to cortex and striatum (not in spec)
Summarise where GABA is used in the basal ganglia system.
[IMPORTANT]
- From striatum to the internal globus pallidus (+ substantia nigra pars reticulata) and external globus pallidus
- From external globus pallidus to the subthalamic nucleus
- From internal globus pallidus (+ substantia nigra pars reticulata) to the thalamus and brainstem nuclei
Summarise where dopamine is used in the basal ganglia system.
[IMPORTANT]
From substantia nigra pars compacta to striatum
Which synapses in the basal ganglia are important in reinforcement learning in movement?
Corticiostriatal synapses, which undergo plasticity
Which parts of the thalamus does the internal globus pallidus/substantia nigra pars reticulata output to?
Ventral anterior and ventral lateral thalamic nuclei.
(VA and VL)
What are some brainstem nuclei that the internal globus pallidus and substantia nigra pars reticulata ouput to?
[EXTRA?]
- Superior colliculus
- Reticular formation
- Pedunculopontine nucl.
- Habenular nucl.
Describe the principle by which the basal ganglia feedback on the cortex (allowing them to perform their function).
- When the striatum is excited by glutamate from the cortex, it releases GABA on the substantia nigra pars reticulata/internal globus pallidus
- This in turn reduces firing of the substantia nigra pars reticulata/internal globus pallidus, so that there is less inhibitory GABA signalling onto the thalamus
- This increases firing in the thalamus, so it stimulates the cortex
- If the substantia nigra pars reticulata/internal globus pallidus is stimulated instead by the subthalamic nucleus, the opposite happens and the thalamus/cortex is inhibited
Therefore, the basal ganglia perform cortical feedback via disinhibition.
Give some experimental evidence for how the basal ganglia feedback on the cortex.
[EXTRA]
(Deniau & Chevalier, 1984):
- Stimulated the striatum using glutamate
- Measured the activity at:
- (1) Substantia nigra pars reticulata/internal globus pallidus -> This showed that there was decreased activity caused by release of GABA from the striatum
- (2) Thalamus -> This showed that there was increased activity caused by decreased release of GABA from the substantia nigra parts reticulata/internal globus pallidus
- Thus, this showed that the basal ganglia feedback on the cortex via a process of disinhibition
What are the two main pathways of transmission through the basal ganglia?
[IMPORTANT]
- Direct pathway (1) -> Passes from the striatum to the substantia nigra pars reticulata/internal globus pallidus
- Indirect pathway (2) -> Passes from the striatum to the external globus pallidus to the subthalamic nucleus to substantia nigra pars reticulata/internal globus pallidus to the
There is also the hyperdirect pathway (3), which bypasses the striatum entirely, but this is not mentioned in the spec.
Can the neurons in the striatum that pass to the direct and indirect pathway be mapped?
No, they are all interspersed throughout the striatum.
Which neurons in the basal ganglia are dopaminergic?
Substantia nigra pars compacta
What sort of pathway is the nigrostriatal pathway?
Ascending dopaminergic
Describe the concept of various basal ganglia loops.
[EXTRA]
- The substantia nigra in the midbrain is topographically mapped, so that different parts receive input from different parts of the striatum, which in turn receives input from different parts of the cortex
- These loops may have different functions
- Pre-motor and motor loops involve:
- Pre-motor and motor cortex
- Dorso-lateral striatum areas
- Lateral substantia nigra
- Limbic loops involve:
- Orbital and medial prefrontal cortex
- Ventro-medial striatum areas
- Medial substantia nigra
- Cognitive/associative loops are between these two
- Note that these pathways loop back to the cortical areas via the thalamus
Which basal ganglia pathway do D1 and D2 striatum neurons link to?
- D1 -> Direct
- D2 -> Indirect
Summarise the functions of the direct and indirect pathways.
[IMPORTANT]
Direct (1):
- The striatum releases GABA on the substantia nigra pars reticulata/internal globus pallidus
- This in turn reduces firing of the substantia nigra pars reticulata/internal globus pallidus, so that there is less inhibitory GABA signalling onto the thalamus -> i.e. There is disinhibition
- This increases firing in the thalamus, so it stimulates the cortex
- Thus, it facilitates movement
Indirect (2):
- The striatum releases GABA on the external globus pallidus
- This in turn reduces firing of the external globus pallidus, so that there is less inhibitory GABA signalling onto the subthalamic nucleus
- This increases glutamate release onto the substantia nigra pars reticulata/internal globus pallidus
- This increases substantia nigra pars reticulata/internal globus pallidus firing, so it inhbits the thalamus and thus inhibits the cortex
- Thus, it inhibits movement
What effect does dopamine release on the striatum have?
[IMPORTANT]
- Dopamine is excitatory at D1 receptors, so it stimulates the direct pathway
- Dopamine is inhibitory at D2 receptors, so it inhibits the indirect pathway
Since the indirect pathway is inhibitory, the dopamine leads to an increase in movement via both pathways.
Give some experimental evidence for the distrubution and function of D1 and D2 neurons in the striatum.
- Expression of GFP in either D1 or D2 neurons (Gerfen, 2011)
- Optogenetics to explore the consequences on mouse movement of stimulating either D1 or D2 neurons -> D1 stimulation leads to more movement (Kravitz, 2010)
What are some examples of basal ganglia diseases?
- Parkinson’s disease [IMPORTANT]
- Drug-induced parkinsonism [IMPORTANT]
- Huntington’s disease [IMPORTANT]
- Hemiballismus [IMPORTANT]
- Multiple system atrophy
- Tourette syndrome
- Dystonias
- Manganism
- Sydenham’s chorea
- Wilson’s disease
- Hatters disease
- Hallevorden Spatz
- Tardive dyskinesia
What are the symptoms of basal ganglia
There can be either:
- Deficiency of movement -> e.g. Akinesia, Bradykinesia
- Involuntary movements -> e.g. Tremor at rest (contrast with cerebellum), chorea, athetosis/dystonias, ballismus, tics, stereotypies, dyskinesias, hyperactivity
The symptoms vary with disease and site of problem.
Compare the tremors seen in basal ganglia and cerebellum disease.
- Basal ganglia -> Tremors at rest
- Cerebellum -> Tremors during movement
What is chorea?
Involuntary dance-like movements seen in basal ganglia diseases.
What are dystonias?
Involuntary twisting or writhing movements of the limbs, seen in basal ganglia diseases.
What is ballismus?
Involuntary irregular flinging movements seen in basal ganglia diseases.
What is the prevalence of Parkinson’s disease?
The second most common neurodegenerative disorder after Alzheimer’s (1% prevalence over 60 yrs, 5% over 85 yrs).
Who discovered Parkinson’s disease?
James Parkinson (1817)
What is the age of onset of Parkinson’s disease?
5th or 6th decade
What are the symptoms of Parkinson’s disease?
- Motor symptoms (TRAP):
- Tremor at rest [IMPORTANT]
- Rigidity [IMPORTANT]
- Akinesia (hypokinesia, bradykinesia) [IMPORTANT]
- Postural instability
- Problems with sleep behaviour (RBD)
- Non-motor dynsfunction:
- Olfaction
- Bowels
- Depression
- Pain
- Cognition
- Motivation
- Dementia
Draw a diagram to show the progression of Parkinson’s disease.
What acronym can be used to remember the motor symptoms of Parkinson’s disease?
TRAP:
- Tremor at rest
- Rigidity
- Akinesia (hypokinesia, bradykinesia)
- Postural instability
What is the mechanism of Parkinson’s disease?
[IMPORTANT]
- Progressive loss of dopaminergic substantia nigra pars compacta neurons
- This means there is a loss of dopaminergic control of the striatum, which is usually required to promote movement
How does Parkinson’s disease present in histology?
There is the loss of the black stripe in the midbrain (caused by the loss of the substantia nigra neurons).