Lecture 7 Flashcards
(34 cards)
What is important during a reflex?
Only contracting one of the muscles and not the other
What is feedback control?
Controlling muscle due to input about task currently being carried out
What is feedforward control?
Controlling muscle due to input about task about the be carried out
What is the somatotopic map?
Neurons project to groups of muscles from a specific region of the primary motor cortex for coordinated action
What affect does stimulation of the PMC have?
Signal sent down the spinal cord to the alpha-motor neurons which send signal out to the periphery
What is the major pathway in voluntary movements?
Starts in association starts the action potential, travels through the caudate and patamen (which has inputs from the substantia nigra), then the globus pallidus, then the thalamus and finally the motor cortex
What is common between the PMC and other parts of this pathway?
They are all spatially mapped
Outline the signalling pathway from the assoication cortex
Stimulates the caudate/putamen which inhibits the globus pallidus, causing signalling from the thalamus to the motor cortex. Caudate/putamen also receives dopaminergic signals from the subsatntia nigeria which can be both inhibiting and excitative
Also an indirect pathway which involves the subthalamic nuclei
What are the symptoms of Huntington’s disease?
What is the cause?
Fast jerky movements
Due to gaining CAG (glutamine) repeats on chromosome 4, affecting synaptic transmission, by reducing transport of vesicles. Less inhibition of the thalamus and increased excitation of the cortex.
What are the symptoms of Parkinson’s disease?
Hard to initiate and maintain movements (Bradykinesia)
What is Parkinson’s disease associated with?
Death of dopaminergic substantia nigra neurons, and these dying cells have Lewy bodies
What are Lewy bodies?
What do they do over time?
Accumulation of α-synuclein and ubiquitin; trying the degrade by ubuitination but the bundle of α-synuclein too large, firstly in axons but then in cell bodies
Start in the substantia nigra but then spread to other regions; including the cortex (prion like)
What was shown using fetal grafts?
Fetal grafts cured Parkinson’s disease, however, postmortem they were also shown to have Lewy bodies; so they are spreading
Why is the substantia nigra black?
They express melanin
Why is the bradykinesia occurring?
Degeneration of substantis nigra leads to tonic inhibition of thalamus and decreased excitation of the cortex
What therapies exist?
- L-DOPA; dopamine precursor which is able to cross the BBB (only works for 5-7 years)
- Dopamine agonists
- MAO-B inhibitors; stop dopamine degradation
- Cell replacement; fetal midbrain, pigs, carotid body, stem cells
- Deep brain stimulation
What role does the carotid body play?
Oxygen sensor; but due to degeneracy of sensors it can be removed and not have a large effect
What occurs due to over use of L-DOPA?
How can it be treated?
Dyskinesia develops; impairment of voluntary movement
Possibly due to the dopamine being used by serotonin neurons
Give 5-H agonists to stop serotonin
How does Deep brain stimulation work?
Not known; proven not to be inacitvation of STN neutrons, affects on STN axons or acitvation of the STN output.
Possibly due to reduction in burstiness; reducing β-rhythmical between STN and cortex
What pharmacological mimics can cause PD?
6-OH dopamine and MPTP (metabolised to MPP+) both cause destruction of dopaminergic neurons
How does MPTP(MPP+) cause damage in animal models?
Damages the neurons; (1)activating microglia, which produce nitric oxide and (2)causes wnt signalling which further damages the neuron. Creating positive feedback loop.
What environment factors can cause PD?
Paraquat Rotenone (fish poison); blocks mitochondrial function and upregulates α-synuclein
What symptom order supports the Braak hypothesis?
Gastric start, then movement disorders and then psychiatric symptoms
As the Lewy bodies spread
What are the genetic causes?
Very rare inherited forms by mutations in
- α-synuclein (folds SNAREs)
- Parkin (E3 ubiqutin ligase)
- DJ-1 (Stress response chaperone)
- PINK-1 (Mitochondiral protien kinase)
- LRRK2 (Mitochondiral protien kinase)
