Lecture 3 - Motor Control, Dopamine and Basal Ganglia Flashcards
What are the 4 motor Related structures in CNS
Key structures involved in movement and motor control:
- Motor Cortices
- Basal Ganglia (also known as striatul complex)
- Cerebellum
- Spinal Cord
What makes up the motor cortices?
Cortical Motor Areas:
- Primary Motor Cortex (M1)
- Premotor Cortex (PMC)
- Supplementary Motor area/ cortex (SMA)
Outline the Primary Motor Cortex
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- Known as the M1
- Large Pryamidal output neurons (Betz cells)
- Most of the axons (85%) go into contralateral spinal cord for direct motor control
- associated with fine, discrete movements
- contralateral means to the other side
- Direct motor control via spinal cord efferents
Outline the Premotor Cortex/ Area
- Also known as the PMC/ PMA
- Helps you respond to stimuli
- Output mainly to M1
- These neurons are to do with ANTICIPATED MOVEMENTS - planning movements
- Prepares M1 for planned movements
- lesion lead to slowing of anticipated movements but not paralysis
Outline Somatotropic Organisation of M1
- For each different party of body, there is a different area of the motor cortex activated (from brain scans)
- Disproportionate amount of motor cortex devoted to fingers and speech muscles (lips, larynx etc)
- More neurons and more energy required = larger area dedicated to it
Outline the Supplementary Motor Area
- Ouput again mainly to M1
- For Complex movements, like the ones that use several muscles or which cross the sides of the body
- Complex voluntary movements (playing piano) but not for simple acts
- even if that movement is just imagined its activated
- Lesions inhibit ability to perform complex movements
Complex motor plan rehersal
What do SMA and PMA do then?
Prepare M1 for complex movements
What other information does the SMA & PMA use
Whilst doing a complex movement like running down the wing in footbal, SMA & PMA use:
- Visual information: looking when pass is coming
- Auditory: someone shouting your name
- Where we are in space and time
SMA & PMA constantly monitoring this and feeding it back to the M1
Outline the roles (4) of the cerrebellum
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Basically takes all this information and relays it to the spinal cord, where the instructions are sent to
- so it can do these quick reflexes but also skilled movements
- Postural reflexes - if you dont have time to loop all this information around the brain, it just goes straight from here to spinal cord
- Rapid skilled limb movements
- Integration of movement sequences
- Motor Learning
- from comparing expected sensory feedback to actual feedback
What are the damage effects on the cerrebellum
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Cerebellar Ataxia
- Posture and balance disturbance
- Limb rigidity (smooth movement of seperate joints, but it is staccato and not integrated)
- Poor timing of ballistic (rapid, aimed) movements (throwing ball, kick ball etc)
What are the 4 components of the Basal Ganglia or (Straitul complex)
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- Caudate Nucleus - these first two overlay everthing
- Putamen -
- Globus Pallidus (has a lateral and medial (outside and inside))
- Substantia Nigra (at bottom, feeds DA into the system)
Thalamus is between 2 tails of the caudate
What is the Basal Ganglia important for?
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Critical for selecting motor plans and initiating movement
- planning and initiating movements
What are the inputs to the Basal Ganglia
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- Primary Motor + Somatosensory Cortex (using glutamate)
2. Substantia Nigra (Dopamine)
What are the outputs to the Basal Ganglia
- Back to M1, PMA and SMA (Via thalamus)
2. brainstem motor nuclei via ventrodmedial pathway - for automated movements
What are the 2 processing routes involved in the Basal ganglia
- Direct (excitatory)
- Indirect (inhibitory)
Movement requires a balance of excitatory and inhibitory stuff
Outline the Direct basal Ganglia processing route
- Cortex (glutamate - excitatory)
- Putamen (GABA - inhibitory)
- Globus Pallidus Internal (GABA - inhibitory)
- Thalamus (Glutamate - excitatory)
- Back to Cortex
Overall the direct route is excitatory
Stimulated by dopamine input to the Putamen from substantia nigra, via D1 Receptors
- D1 receptors are an excitatory family, they accept excitatory input
Outline the indirect basal Ganglia processing route
- Cortex (gluatmate - excitatory)
- Putamen (GABA- inhibitory)
- Globus Pallidus External (GABA - inhibitory)
- SUB-THALAMIC NUCLUES (glutamate - excitatory)
At this point rejoins the direct route:
- Back to the Globus Pallidus Internal (GABA)
- Thalamus (Glutamate)
- Back to cortex
Overall the indirect route is inhibitory
Suppressed by dopamine input to putamen, from substantia nigra, via inhibitory D2 Receptors
- longe route, Dopamine suppresses the routes with D2 receptors
What controls the balance between these two routes?
Dopamine input to the Putamen from the Substantia Nigra control balance
Need a balance because if we had too much excitatory input (direct), we would move all the time
- need the indrect route to return movements to resting states
What type of receptor are dopamine receptors
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Metabotropic receptors
- G-protein coupled
- not directly linked to Ion channels
Outline the D1 Family of dopamine receptors
D1 family is made up of:
- D1 Receptors
- D5 Receptors
These are excitatory
- Coupled to Gsa (Second messenger protein) GS ALpha
- this activates the process of ADENYLYL CYLCASE
- This increases intracellular second messenger cAMP (Cyclic Adenosie Monophosphate)
Outline the D2 Family of dopamine receptors
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D2 Family is made up of:
- D2 Receptors
- D3 Receptors
- D4 Receptors
These are inhibitory
- Coupled to Gia (second messenger protein) Gi alpha
- This inhibits adenyly cyclase
- Reduces intracellular second messenger cAMP
Which part of the Basal Ganglia Processing route is most important?
Dopamine Goes from :
- Substantia nigra to
- putamen
Putamen is very important, because it has both D1 receptors and D2 receptors
- At this point it can go either way
- can be excitatory (direct route) or inhibitory (indirect route)
We can use the same neurotransmitter to inhibit or excite the system
What are the motor symptoms of Parksinsons Disease
• Resting tremor, ‘pill rolling’ hands
- old people may have a tremor, but this is pill rolling
•Muscular rigidity and stiff limbs
• poor balance, slow movement
- e.g. writing becomes spider like, cant control fine movements
• Problems initiating/ regulating movement sequence
- starting/ stopping movement, and postural balance
- might be able to initiate but not regulate or not be initiate at all
What are the mood/cognitive symptoms of Parksinsons Disease
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• Can often start with a depression (40-50% of cases) • Anxiety disorder also common, 1 in 4 - perhaps hallucinations •Cognitive problems, memory, attention - can have 'Parkinsons with dementia'
What is cause of Parkinsons?
Caused by neuron loss in Substantia Nigra
- leads to a lack of dopamine in the putamen
What is treatment for Parksinsons?
L-dopa (DA precursor)
What are side effects of L-Dopa
•Dyskensia/ Dystonia
- involuntary movements and postures due to too much DA in putamen, similar to Huntingtons
Outline Lewy Body Dementia
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- Flucuating attention, not always alert, concious seems to fluctuate
- Second most common dementia
- Lewy bodies in CNS cells, predominantly in brain
- Hallucinations
- issues with language and planning
- Shown by Trail Making Test B
What are symptoms of huntingdons disease?
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•Uncontrollable movements
- not planned, coordinated or controlled
- jerky limbs:CHorea
- often mistaken for being drunk/ mad
- cant stay seated
- Usually starts around 20-40
- progressive, eventually fatal after around 20 years
What are causes of huntingtons?
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• Rare genetic mutation in huntington gene
• Cell loss in caudate nuclues & Putamen
- means the indirect route is weaker, and the direct route is stronger
- weak indirect means you cannot inhibit movements
- much more activation in Basal Ganglia - leading to involuntary movements
What are treatments for huntingtons?
- Various drugs to manage symptoms
- no long term cure: its progressive
What is the difference in where things are wrong in Parkinsons compared to huntingtons?
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Parkinsons:
- Substantia Nigra is broken - not sending dopamine to either inhibitory or excitatory systems
- not much dopamine going to Putamen
- no dopamine mean input = cant initiate movement
- lack of movement
huntingtons:
- Caudate and Putamen is broken
- making excitatory route much stronger
- Link between D2 and Gpe is broken too
- D1 route is much stronger - cant control it
What is Dopamine Critical for?
Motor regulation
- critical in regulating movement
- in the basal ganglia
- Produced in Substania Nigra
What are the other roles in the brain of Dopamine?
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- Cognitive function & memory (ageing)
- Mood
- Hallucinations, psychosis, Sz
- Reward Systems (VTA -> Nuclues Accumbens)
- Target for recreational drugs - because of reward systems, its the happy NT
What can too much dopamine cause?
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Over time, the body becomes used to it, and doesnt produce any
- so you get ticks/ tardive dyskenisia and chorea type movements
- have to lower Da down but the person returns to parkinsons symptoms
Outline Dopamine Synthesis
- Phenylalanine
- Tyrosine (starts as an amino acid)
- Dopa (now a neurotransmitter)
- Dopamine
- Norepinephrine
- Epinephrine
Why do you have to give a parkinsons patient L-dopa
- Dopamine cant pass the blood brain barrier
- have to give a precursos that can - l-dopa
- Have to hope it will be converted into dopamine, but if their system is so broken, it might not happen
Whats bad about synthesis/ giving l-dopa
1: Free Radicals
- Synthesis generates other stuff as well as Dopamine, compounds that can damage DNA// damage cells are a byproduct
- these are called free radicals
- can cause Az or accelerate ageing
2: Oxidative stress
- too much dopamine/ L-Dopa and brain gets stressed trying to use it all
- Might accelerate ageing
- or worsen Parkinsons symptoms
