Lectures 1-3 (Paul Kasher) Flashcards
Introduction to motor systems, muscle contraction mechanism and motor units
What are the three types of Motor behaviour?
Week 1- Introduction to Motor systems
- reflexes
- rhytmic movements
- voluntary movements
What are some key features of reflexes/reflexive movement?
(Name 4 features)
Week 1- Introduction to Motor systems
Reflexes are
* Involuntary
* unconcious
* usually elicited by peripheral stimuli
* consist of organised patterns of muscle contractions & relaxations
What type of muscle contractions are featured in reflexes and what are these contractions dependent on?
Week 1- Introduction to Motor systems
Reflexes involve spatial & temporal patterns of muscle contractions
These contractions are dependent on the type of sensory receptors stimulated and the strength of the stimuli
What are Rhythmic movements? Give examples.
Week 1- Introduction to Motor systems
Typically pattern based movements such as breathing, chewing and running
What happens to muscles in Rhythmic movements?
Week 1- Introduction to Motor systems
The muscles often alternate contractions and relaxation on both sides of the body.
What primarily controls Rhythmic movements?
Week 1- Introduction to Motor systems
Circuits in the spinal cord (which are often entrained by a peripheral stimulus)
How do Rhythmic movements occur? (not the mechanism, but the onset)
Week 1- Introduction to Motor systems
They can occur spontaneously (e.g via voluntary movement)
What makes voluntary movements different from reflexive and Rhythmic movements?
(Name 2)
Week 1- Introduction to Motor systems
- They self initiated - under concious control
- They get more accurate with practice (e.g a toddler learning to walk)
When may someone engage in a voluntary movement?
Week 1- Introduction to Motor systems
- When attempting to accomplish a task (e.g typing a text message)
- ^ they can also be triggered by an external event (e.g positioning yourself to catch a ball)
What are the two control systems that the nervous system uses in order to deal with the physical world?
Week 1- Introduction to Motor systems
- feedback control
- feedforward control
Define feedback control
Week 1- Introduction to Motor systems
the nervous sysem uses sensory signals from the body to monitor limb positioning. By using sensory feedback signals, the position and tension in limbs can be modified as needed
Define feedforward control
Week 1- Introduction to Motor systems
nervous system anticipates future events based on prior experience (memory), initiating pre-emptive strategies based on this experience
Describe what is happening during feedback control
(3 points)
Week 1- Introduction to Motor systems
- A reference signal exists, representing the body’s desired state and compares it to the signals from sensors in the muscles and joints
- the signals from the sensors tell us what the current state of the body is
- Any difference between these two pathways (i.e an error signal) is used to adjust the muscles to minimise this error
Using the example of catching a ball
Outline the process of feedback control
Week 1- Introduction to Motor systems
- When catching a ball, we have a desired state (being stable and actually catching the ball)
- Feedback control via sensory feedback muscles compares our current state to the desired state (Are we off balance? Do we have a secure hold of the ball?)
- If a difference exists, an error system kicks in, controlling or amplifying body movements in order to reach the desired state (such as activation of stabiliser muscles or tightening your grip on the ball)
What determines feedback control?
Week 1- Introduction to Motor systems
Gain - gain determines the efficacy of feedback systems
What is Gain?
Week 1- Introduction to Motor systems
A dynamic system that controls for execution error when processing sensory input
How can gain systems be altered and what is this called?
Week 1- Introduction to Motor systems
- Can be altered by providing more (or less) ‘signal’ in order to correct for errors
- this is known as fine tuning
What determines whether a feedback signal is attenuated or amplified?
Week 1- Introduction to Motor systems
Whether the infomation contributes to or distracts from reaching a goal
Why is gain reduced in some cases?
Week 1- Introduction to Motor systems
For stability as well as filter disruptive or self generated feedback
Why is gain enhanced in some cases?
Week 1- Introduction to Motor systems
To facilitate online motor control and movement adaptation
What are the two categories of pathologies that affect feedback and gain systems?
Week 1- Introduction to Motor systems
- High gain pathologies
- low gain patholgies
Outline three features of high gain pathologies
Week 1- Introduction to Motor systems
- Rapid to correct errors
- Vulnerable to environmental changes & long delays
- Prone to over correction and thus can lead to further error (oscillations)
Outline three features of low gain pathologies
Week 1- Introduction to Motor systems
- Slower to correct errors
- Less oscillatory behaviour
- Most of our physiological feedback control is via low gain (e.g postural feedback)
What is the take home message of sensory gain?
( as in what does it allow us to do)
Week 1- Introduction to Motor systems
It allows animals to fine tune the impact that feedback info has on motor behavioural output
( he said this was really important in the lecture)
Outline the key components of feedforward control
(name 2)
Week 1- Introduction to Motor systems
- Control acts in advance of certain pertubations (deviations of a system/differing from the norm)
- experience is very important
Using catching a ball as an example
Outline the process of feedforward control
(four major points)
Week 1- Introduction to Motor systems
- you see that you want to catch a ball
- the sensory unit detects this and the visual system would send the correction signal to the brain, causing feedforward input
- when planning to catch the ball, the feedforward mechanisms amplify a signal to the hand, causing both the agonist and antagonist muscles surrounding the elbow joint to contract
- this process is learned from experience as the outcome of stiffening the elbow joint, supprsses the stretch reflex caused by the weight of the ball
Using catching a ball as an example
When does feedback occur
Week 1- Introduction to Motor systems
cutaneous receptors in the hand and arm muscles send feedback only after the ball has landed in your hand
Using catching a ball as an example
What normally happens directly after you catch the ball and how does feedforward input compensate this
Week 1- Introduction to Motor systems
- Normally, the rapid stretch of a muscle would evoke a stretch reflex (controlled by spinal circuits)
- this is a protective reflex which opposes the overstretching of muscles
- feedforward input causes stiffening at the elbow joint in order to suppress the stretch reflex
Imagine you are looking at an EMG of someone catching a ball
What would you expect to see when the ball is dropped and when the ball is caught?
Week 1- Introduction to Motor systems
- When the ball is dropped (even without it in hand), the muscles start contracting in anticipation.
- When the ball impacts the arm, there is further stabalisation of the muscles in the arm due to further contraction
(There is an image on the slides which shows this well)
Imagine you are looking at an EMG of someone catching a ball
What three key principles of feedforward control does catching a ball show?
Week 1- Introduction to Motor systems
- Feedforward control is critical for fast movements
- It relies on nervous systems ability to predict the future based on past experienves
- Feedforward control starts in the cortex, feedback control starts in the muscle, and the two systems interact in the spinal cord
What are the two features of the functional organisation of the motor control systems that make them work well?
Week 1- Introduction to Motor systems
- Motor control is hierarchical and distributed between the spinal cord, brainstem and forebrain
- sensory info is processed dynamically and in parallel systems to motor info, allowing it to influence the evoloution of a movement
What is the order of the hierarchy within the motor control systems
(three levels - descending control)
Week 1- Introduction to Motor systems
Cortex is the highest level
Brainstem is the middle level
Spinal cord is the lowest level
What is the role of the spinal cord in the hierarchy of motor organisation
Week 1- Introduction to Motor systems
- It contains circuits for both reflexive and rhythmic movements
- spinal motor neurons are the ones to execute movement
What is the role of the brainstem in the hierarchy of motor organisation
Week 1- Introduction to Motor systems
It contains two descending pathways to project to the spinal cord
In regards to motor organisation
What are the names of the two descending pathways in the brainstem
Week 1- Introduction to Motor systems
Medial descending system & Lateral Descending system
In regards to motor organisation
What is the role of the medial descending system
Week 1- Introduction to Motor systems
- a system of the brainstem that primarily deals with the core muscles of the body & its involved in postural control
- does this by influencing the activity of circuits in the spinal cord
In regards to motor organisation
What is the role of the lateral descending system
Week 1- Introduction to Motor systems
- A system of the brainstem that primarily deals with distal muscles and involuntary goal directed movements
- does this by influencing the activity of circuits in the spinal cord
What is the role of the cortex in the hierarchy of motor organisation
Week 1- Introduction to Motor systems
- Primary motor cortex & multiple premotor areas regulate activity in the brainstems descending tracts as well as projecting directly to the spinal cord
In regards to motor organisation
What role do the Cerebellum and basal ganglia play in motor control
Week 1- Introduction to Motor systems
Regulating, planning and coordinating various muscles during voluntary movements via the thalamus
What kinds of areas project to the motor cortex
Week 1- Introduction to Motor systems
- multiple cortical areas project to the motor cortex (Prefrontal, parietal and temporal association areas)
What are the three types of muscle
Week 1 - Muscle Contraction Mechanisms
Smooth muscle,cardiac muscle, skeletal muscle
(Skeletal muscles are the ones involved in movement
Outline some functional groups of muscles and give very brief descriptions
(5 groups, one with some subdivision)
Week 1 - Muscle Contraction Mechanisms
- Prime mover (agonist) - main muscle
- antagonist - work in opposite directions
- synergists- work together
- fixators - stabilise
- flexors,extensors, abductors, adductors - coordinate direction of action
what is a muscle fibre
Week 1 - Muscle Contraction Mechanisms
A single cell
How many myofibrils can a single muscle fibre contain
Week 1 - Muscle Contraction Mechanisms
100-1000s
What surrounds a myofibril and what does this do
Week 1 - Muscle Contraction Mechanisms
Sarcoplasmic reticulum -used for calcium storage/release
What is a Sarcomere
Week 1 - Muscle Contraction Mechanisms
- A unit of a myofibril
- The smallest contractile unit in a muscle fibre
What are sarcomeres comprised of
Week 1 - Muscle Contraction Mechanisms
Interdigitated thick and thin filaments, bounded by Z-disks
(Interdigitated = interlocked like fingers)
Up to how many sarcomeres are contained in a single myofibril
Week 1 - Muscle Contraction Mechanisms
20,000 (as repeated unitsalong its length)
How are thick and thin filaments arranged in a sarcomere
Week 1 - Muscle Contraction Mechanisms
Thin filaments project both directions from Z bands, thick filaments project from the centre
What are thin filaments
(As in structure and composition) (name 3 elements)
Week 1 - Muscle Contraction Mechanisms
- composed of F actin
- arranged as a helix
- along this helix there is tropomyosin and troponin
What are thick filaments
(as in structure and composition)
Week 1 - Muscle Contraction Mechanisms
- composed of 250 myosin molecules
- myosin molecules have a long body and globular heads
(myosin looks a bit like a golf putt)
In reference to the sarcomere
What are connectins
Week 1 - Muscle Contraction Mechanisms
- Fine, thin elastic filaments, connecting ends of thick filaments and z-disks
- give muscles their spring-like property
In reference to the action of thick and thin filaments
What is the sarcomere like in resting state
Week 1 - Muscle Contraction Mechanisms
- Thick filaments protude outwards
- theres an immediate overlap between the thin and thick filaments
In reference to the action of thick and thin filaments
What happens to the sarcomere during a muscle contraction
Week 1 - Muscle Contraction Mechanisms
- there is maximal overlap between the thick and thin filaments, producing cross bridges between each other, allowing the filaments to slide over one another
- this pulls the z lines of the sarcomere closer together, shortening the myofibril and thus the muscle
What are the 5 steps of sliding filament theory
Week 1 - Muscle Contraction Mechanisms
- Rest
- activation
- sliding of filaments
- myosin detachment
- reaction of myosin
What are examples of contractile proteins
Week 1 - Muscle Contraction Mechanisms
Myosin (thick) and actin (thin) filaments
What happens in step 1 (rest) of sliding filament theory
(4 major points)
Week 1 - Muscle Contraction Mechanisms
- Troponin and tropomyosin complexes on thin filaments block the binding sites on the actin
- On the thick filaments, the myosin heads are ADP bound (and are in a cocked position)
- there is low calcium in the sarcoplasm (~10^-7 to 10^-8 M), so theres no activation
- There are no cross bridges between thin and thick filaments
What happens in step 2 (activation) of sliding filament theory
(5 major points)
Week 1 - Muscle Contraction Mechanisms
- Muscle fibre is activated (APs travel down t-tubules)
- Calcium is released from the cisternae in the sarcoplasmic reticulum (SPR)
- Calcium binds to troponin in the troponin myosin complex
- ^ In doing so, the conforamtional change in the thin filament exposes the actin binding sites
- Attachment of cocked myosin heads = cross-bridge formation
What happens in step 3 (sliding of filaments) of sliding filament theory
(3 major points)
Week 1 - Muscle Contraction Mechanisms
- mechanical energy (from ATP dephosphorylation) stored in ‘cocked’ myosin heads is released → causing a power stroke
- Longitudinal force pulls the thin and thick filaments into greater overlap (~0.06 µm) → shortening the muscle fibre
- Myosin heads have now shed their bound ADP → they can resume a relaxed state but remain cross linked to thin strand
Week 1 - Muscle Contraction Mechanisms
What happens in step 4 (Myosin detatchment) of sliding filament theory
(2 major points)
Week 1 - Muscle Contraction Mechanisms
- ATP binds to myosin heads which then detaches from its actin binding site
- Actin binding site is released and can form another cross-bridge to sustain muscle contraction
What happens in step 5 (Reactivation of Myosin) in sliding filaments theory
(various things happen depending on the [Ca2+] )
Week 1 - Muscle Contraction Mechanisms
Thick filaments:
* energy is released by dephosphorylation of ATP to bound ADP is stored in myosin heads → myosin heads are re-cocked
Thin filaments:
* High calcium conc conditions: system remains activated (back to step 2), muscle contraction persists
* In low calcium conc conditions: theres a return to resting state (back to step 1): Myosin heads are cocked but unable to form cross-bridge
What is the Sarcoplasmic Reticulum (SPR) ?
Week 1 - Muscle Contraction Mechanisms
- A network of longitudinal tubules and chambers contained within muscle fibres
- at rest, intracellular calcium conc is low, so its actively pumped into the SPR
In reference to the Role of Ca2+ in excitation-contraction coupling
What is the ‘path’ calcium takes within a muscle fibre
Week 1 - Muscle Contraction Mechanisms
- Ca2+ is released from cisternae of SPR
- Ca2+ diffuses along myofibrils
- Ca2+ binds to troponin enabling cross-bridges to form
In reference to the Role of Ca2+ in excitation-contraction coupling
Outline the speed of release and reuptake of calcium
Week 1 - Muscle Contraction Mechanisms
Both are rapid
(release is 20-50ms to activate the thin filaments fuly, reuptake is 80-200ms in order to see the decrease in cross bridges)
What does a low frequency of APs in a muscle indicate indicate
Week 1 - Muscle Contraction Mechanisms
- A muscle twitch
- Limited Ca2+ release
- Enough time for Ca2+ reuptake/ relaxation
What does a high frequency of APs in a muscle indicate
Week 1 - Muscle Contraction Mechanisms
- tetani ( a series of contractions that start before the last one can fully finish)
- More Ca2+ is released
- Less time for Ca2+ reuptake
- Summation/ fusion
What are tetani associated with
(think unfused and fused)
Week 1 - Muscle Contraction Mechanisms
Unfused - sometimes used for lifting
fused/sustained -associated with disease
What two things can influence the amount of force developed by a muscles
Week 1 - Muscle Contraction Mechanisms
- frequency of APs
- the overlap between thick and thin muscle filaments prior to stimulation (i.e length-tension relationship)
What is maximal stretch
Week 1 - Muscle Contraction Mechanisms
When there are very few or no overlapping thick and thin filaments
What is the length tension relationship dictated by
Week 1 - Muscle Contraction Mechanisms
- the number of actin:myosin bridge connections available
What happens if the muscle fibres are too stretched , too contracted and at optimal length
Week 1 - Muscle Contraction Mechanisms
- too stretched= less cross bridges = less force
- Too contracted = all available bridges occupied = no additional force possible
- Optimal length = optimal overlap between myosin and actin
What are ‘Red Muscles’ and what are they used for
(give 2 examples of actions that use red muscles & 3 features)
Week 1 - Muscle Contraction Mechanisms
(anti-gravity/postural) – standing, walking
- mainly slow-twitch muscle fibres (type I fibres)
- can sustain small amounts of tension for long periods (resistant to fatigue)
- aerobic metabolism, many mitochondria and capillaries, myoglobin rich
What are ‘Pale muscles’ comprised of and what are they used for
Week 1 - Muscle Contraction Mechanisms
- Mix of fast-twitch (type II) and slow-twitch (type I) fibres
fast twitch fibres divided into: - fast fatigue-resistant (type IIA) fibres - enough aerobic capacity to resist fatigue for a few minutes
- fast fatigable (type IIB) fibres - anaerobic catabolism, use glycogen, forms lactic acid
- used for shorter bursts of activity due to less mitochondria & less myoglobin
What are the three types of muscle fibre?
Week 1 - Muscle Contraction Mechanisms
- slow twitch - type I
- Fast-fatigue resistant - Type IIa
- Fast fatigable -Type IIb/x
IIb and IIx are the exact same theyre just someties called different thi
In reference to pale and red muscles
When comparing non flying birds to birds that fly a long distance, what would expect their muscles to look like
Week 1 - Muscle Contraction Mechanisms
Birds that cannot fly/ fly a short distance will have more pale muscles than birds that fly longer distances who have more red muscles (due to needing more aerobic metabolism and oxygen usage for stamina)
If Using a histological stain to look at the muscle fibres in the calf muscles of an average human, what would you expect to see?
(the stain is looking for ATPase)
Week 1 - Muscle Contraction Mechanisms
- Positive ATPase is dark and negative ATPase staining is light
- Type I muscle fibres are more light whereas type II muscle fibres stained darker
- about a 50/50 split of Type I and type II and random distribution
Outline the primary features of type I fibres
(contraction speed, force, fatigue, recruitment)
Week 1 - Muscle Contraction Mechanisms
- Slow Contraction (50Ms-110ms twitch time) - slow myosin
- Small force (<20g of tetanic tension) - few muscle fibres
- Resistant to fatigue (oxidative metabolism, many mitochondria, good blood supply)
- Recruited first during contraction
Outline the primary features of type IIa fibres
(contraction speed, force, fatigue, recruitment)
Week 1 - Muscle Contraction Mechanisms
- Fast contraction time (25-45ms) -fast myosin isoform
- Intermediate force (20-60g tetanic tension) intermediate number of muscle fibres
- Resistant to fatigue (oxidative metabolism)
- Intermediate recruitment order
Outline the primary features of type IIb/x fibres
(contraction speed, force, fatigue, recruitment)
Week 1 - Muscle Contraction Mechanisms
- Very fast contraction (<10ms) fast myosin isoform
- High force (50-150g tetanic tension) - many, large muscle fibres
- Fatigue easily (anaerobic metabolism, glycogen store, few mitochondria)
- Recruited last during contraction
What are hybrid fibre types
Week 1 - Muscle Contraction Mechanisms
- indicated by recent research- could make up significant proportion of muscle fibres
- express more than one MHC type (I/IIa/IIb)
- training & exercise seemingly enables fibres to shift between hybrid types as well as between fast and slow fibres
What tends to govern the type of muscle fibres someone has
Week 1 - Muscle Contraction Mechanisms
Genetic predisposition (its why long distance runners tend to be east african for example)
What would you expect to see if comparing the muscle fibres of a marathon runner, sprinter and an average person
Week 1 - Muscle Contraction Mechanisms
Average person - 50/50 split of fast and slow fibres
sprinter - more fast than slow fibres
marathon runner- more slow than fast fibres
What is the general size of motor neurons
Week 2 - Motor units
have a cell body of 0.04 - 0.1mm in size and a axon of Up to 1M in length
Outline Upper motor units
(originate→ extend, shape, transmission type,pathways)
Week 2 - Motor units
- Originate in motor/premotor cortex & axons extend down to brain stem or spinal cord
- Pyramidial cells
- Have glutamatergic transmission ( use glutamate as their transmitter)
- Various pathways
Outline Lower motor units
(originate→ extend, shape, transmission type,pathways)
Week 2 - Motor units
- Originate in spinal cord and axons extend down to skeletal muscle (and some glands)
- Some lower motor neurons originate in motor nuclei of cranial nerves in brainstem
- Large neurons, extensive dendritic trees
- Cholinergic transmission
- Final common pathway
Where are Lower motor neuron somas located
Week 2 - Motor units
- Located in ventral horn of spinal cord (and cranial nerve nuclei)
How does convergence of inputs happen in motor neurons
Week 2 - Motor units
There is convergence of inputs from (a) sensory fibres (b) interneurons and (c) descending pathways
How are lower motor neurons organised
Week 2 - Motor units
In motor neuron pools
(MN pool = group of Motor neurons suppling an individual muscle)
What is a motor neuron pool
Week 2 - Motor units
- the group of Motor neurons supplying an individual muscle (e.g. biceps MN pool)
- they are arranged in longitudinal columns of neurons, spanning several (1-4 cords) segments
In reference to motor neuron organisation
What is the proximal-distal rule and what does this mean in terms of muscle development
Week 2 - Motor units
- An organisation principle where medial motor neuron pools in the spinal cord innervate axial/proximal muscles and lateral motor neuron pools in the spinal cord innervate distal muscles
- motor neurons innervating muscles closer to the midline tend to develop & establish connections earlier in development compared to those innervating muscles further from the midline.
- this means that motor neurons controlling movements of the trunk & core (i.e medial motor neeurons) develop before those controlling movements of the limbs
Define motor unit
Week 2 - Motor units
- A motor neuron and the skeletal muscle fibres that it innervates
- forms basic unit of contraction
What do the properties of a motor unit depend on
(two things)
Week 2 - Motor units
neuron and muscle elements
In reference to motor units and muscle fibres
What does the CNS control
Week 2 - Motor units
The CNS controls motor units not single muscle fibres
How many muscle fibres can motor units contain/control , give examples of muscles on the low end and muscles on the high end of this spectrum
Week 2 - Motor units
Between 10s - 1000s
10s example - eye/hand muscles
1000s example - leg/trunk muscles
What is the strength of contraction controlled by
Week 2 - Motor units
- The firing rates of motor units (i.e summation of twitches and tetani)
- recruitment of motor units
In reference to the gradation of muscle force
What function does recruitment serve at low force levels
Week 2 - Motor units
It is a major mechanism at low force levels
What is Hennemans size principle
Week 2 - Motor units
- Small motor neurons are activated/recruited before large motor neurons
- motor neuron recruitment order correlates with the size of their cell body (small before large)
In reference to Hennemans size principle
Why are small motor neurons recruited first?
Week 2 - Motor units
Due to their small surface area which causes two things:
1. high density of synaptic inputs
2. high electrical input resistance
In reference to Hennemans size principle
What is the Ohms law and why is it relevant to motor neurons
Week 2 - Motor units
V (voltage) = I (current) R (resistance)
as smaller motor neurons have a high density of synaptic inputs and a high electrical input resistance, they have a higher EPSP, making them more likely to exceed the threshold for firing APs
Excitatory PostSynaptic Potential (EPSP) = synaptic current x resistance
What (apart from size) differentiates a large motor neuron from a small motor neuron
Week 2 - Motor units
- A large motor neuron produces a much stronger contraction
- a large motor neuron is innervated later (due to its size)
If we have two motor units, one small and one large , which would innervate first and what would happen after the first one has maximally contracted
Week 2 - Motor units
- The small one would innervate first
- The second motor unit would ‘kick in’ (start to contract) after the first one had maximally contracted
In reference to the gradation of muscle force
What does muscle force depend on
(3 things)
Week 2 - Motor units
- the firing rate of motot neurons
- the total number of activated motor units
- the type of activate motor units
In relation to firing rate
What is consistent with all motor neurons
Week 2 - Motor units
They all share a similar firing rate of action potentials (reaching maximal contraction before going back down)
How many motor neurons control a typical muscle
Week 2 - Motor units
100
What is each individual muscle fibre innervated by
Week 2 - Motor units
Normally by A single motor neuron
What is a muscle unit
Week 2 - Motor units
A muscle fibre innervated by a single motor neuron (excluding the motor neuron itslef)
What is the term for the combination of a muscle fibre plus its motor neuron
Week 2 - Motor units
Motor unit
What are the types of motor neuron
(not location, actual structural and functional types)
Week 2 - Motor units
Alpha and gamma (and beta)
(not really gonna cover beta but they exist)
Outline Alpha motor neurons
(muscle fibres supplied, soma size, transmission speed, axon size)
Week 2 - Motor units
- supply extrafusal muscle fibres
- Large soma (50μm diam)
- large (12-20μm) ( ibr idk what this is in reference to)
- fast (CV = 70-120m/s)
- large myelinated axons
( CV = conduction velocity)
Outline gamma motor neurons
(muscle fibres supplied, soma size, transmission speed, axon size)
Week 2 - Motor units
- supply intrafusal (muscle spindle) fibres
- Smaller soma (30μm diam)
- smaller (3-6μm)
- slower (CV =15-30m/s)
- small myelinated axons
( CV = conduction velocity)
What do alpha MNs control
Week 2 - Motor units
Control muscle force generation
What do gamma MNs control
Week 2 - Motor units
Control muscle spindle responsiveness
What are Small Alpha Motor neurons a part of
Week 2 - Motor units
Type S Motor units
(S = slow)
What are some features of Type S motor units
(contraction strength, example of usage, frequency of use)
Week 2 - Motor Units
- weak , sustained contractions
- e.g walking/posture
- Most used
What are intermediate Alpha Motor neurons a part of
Week 2 - Motor Units
Type FR Motor units
FR = Fatigue resistant
What are some features of Type FR motor units
(contraction strength, example of usage)
Week 2 - Motor Units
- moderate contractions
- e.g running
What fibre type/motor unit are Large Alpha Motor neurons a part of?
Week 2 - Motor Units
Type FF Motor units
(FF = Fast fatigue)
What are some features of Type FF motor units
(contraction strength, example of usage, frequency of use)
Week 2 - Motor Units
- powerful,phasic contractions
- e.g jumping
- least used, used sparingly
What types of muscle fibres are S, FR and FF MUs associated with
(MU = Motor unit)
Week 2 - Motor Units
- Type S MU → Type I muscle fibres)
- Type FR MU → Type IIa muscle fibres
- Type FF MU → Type IIb muscle fibres
What are some advantages of the henneman size principle
(name 2 )
Week 2 - Motor Units
1.The non-fatigable muscle fibres are used for most tasks and the fatigable fibres are used sparingly
2.Increments in contractile force (by recruitment of new MUs) roughly proportional to current force
What are the four classifications of motor neuron disease
Week 2 - Motor Units
- Dysfunction of motor neuron cell body (motor neuron diseases)
- Dysfunction of motor neuron axons (peripheral neuropathies)
- Dysfunction of the synapse between MN and muscle fibre (neuromuscular diseases)
- Dysfunction of the muscle fibres (myopathies)
In reference to motor unit diseases
What is an example of a peripheral neuropathy
Week 2 - Motor Units
Guillain-Barre Syndrome (GBS)
In reference to motor unit diseases
What is Guillain-Barre Syndrome (GBS)
(will mostly refer to as GBS in flash cards)
Week 2 - Motor Units
a rapid-onset muscle weakness caused by the immune system damaging the peripheral nervous system
In reference to motor unit diseases
What are some features of GBS
(when it occurs, who it affects, rarity,progressiveness, subtypes?) (5)
Week 2 - Motor Units
- Rapid & progressive, immune-mediated peripheral neuropathy
- Most frequently occurs after an infection, leads to production of antibodies that target peripheral myelin
- Affects men & women of any age
- Rare - 1-2/100k per year
- Heterogeneous condition - at least 7 subtypes that exist w/ some sensory deficits but all share phenotypic overlap
In reference to motor unit diseases
What are some symptoms of GBS
(name 6)
Week 2 - Motor Units
- Numbness, tingling, and pain in distal limbs
- Ascending weakness of legs and arms, affecting both sides of body
- Facial weakness
- Respiratory tract failure
- Paralysis
- Slow recovery (quicker in younger people)
In reference to motor unit diseases
In percentage form, what are the outcomes for people who have GBS
Week 2 - Motor Units
80% patients make full recovery
15% patients left with disability
5% patients die
In reference to motor unit diseases
How is GBS diagnosed
(2 methods)
Week 2 - Motor Units
CSF analysis (cerebrospinal fluid) (raised immune cell protein
Nerve conduction analysis
In reference to motor unit diseases
What are some causes of GBS
(3 points)
Week 2 - Motor Units
- Most commonly caused by bacterial / viral infection
- E.g. Gastroenteritis, Epstein-Barr virus, Zika, Covid??
- B cells aberrantly produce antibodies that target myelin
- Leading to breakdown and damage of myelin sheath, exposing muscle fibre and reduces conduction capacity of motor neuron
- Myelin damage and remyelination reduced conduction capacity of motor neuron -> weakness, paralysis
In reference to motor unit diseases
What are some treatments for GBS
Week 2 - Motor Units
Intravenous immunoglobulins
Plasma exchange (to remove antibodies)
Supportive care and rehabilitation
In reference to motor unit diseases
What is an example of a Neuromuscular Junction disease
Week 2 - Motor Units
Myasethenia Gravis
In reference to motor unit diseases
What does Myasenthenia grais result in
Week 2 - Motor Units
A failure in transmission of signal at NMJ
In reference to motor unit diseases
Outline 3 forms of Myasenthenia Gravis and how prevalent are they
Week 2 - Motor Units
- Autoimmune - (most prevalent): antibodies produced against patients’ own ACh receptor in junctional fold in skeletal muscles
- Congenital (rare): transfer of AChR antibodies across the placenta. Transient.
- Inherited (rare): mutations affecting ACh production and/or signalling
In reference to motor unit diseases
What is the mechanism of all forms of Myasenthenia Gravis?
Week 2 - Motor Units
blocking acetylcholine either by blockage of receptor or reduced production
(more important than knowing how the individual forms do this)
In reference to motor unit diseases
What are some clinical features of Myasenthenia Gravis
Week 2 - Motor Units
- Abnormal muscle fatigue during repetitive / prolonged contraction of cranial muscles (e.g. eyelids, eyes, oropharyngeal). Limb muscles can be affected.
- Remission and relapse phase
- No signs of denervation or muscle wasting (acetylcholine signalling defect rather than a muscle wasting defect)
In reference to motor unit diseases
What treatments ( if any) exist for Myasenthenia Gravis
Week 2 - Motor Units
Drugs preventing ACh degradation can reverse symptoms (e.g ihibition of ACh esterase)
In reference to motor unit diseases
What is an example of a myopathy
(myopathy = dysfunction of muscle fibres)
Week 2 - Motor Units
Duchenne Muscular Dystrophy (DMD)
In reference to motor unit diseases
What is Duchenne Muscular dystrophy (DMD)
Two things
Week 2 - Motor Units
- Progressive skeletal muscle degeneration and weakness
- X-linked recessive disease caused by mutation of dystrophin gene
In reference to motor unit diseases
Who does DMD primarily effect
Week 2 - Motor Units
Boys - its an X-linked recessive disease
(DMD = duchenne Muscular dystrophy)
In reference to motor unit diseases
When does DMD typically present itself what is a common sign
Week 2 - Motor Units
- Presents usually before 5 as awkward walking
- Gowers sign - ask patients to pick themselves up from the flow into an upright position - patients aren’t able to stand up without pushing on their legs
- Also have hypertrophy of calf muscle
In reference to motor unit diseases
What can happen to a patient with DMD in later life
(physical ability & lifespan)
Week 2 - Motor Units
- paralysis in later life
- shortened life span (median life expectancy = 22 years)
In reference to motor unit diseases
What causes DMD
Week 2 - Motor Units
Loss of function mutation in the dystrophin gene
(Dystrophin is an X-linked gene)
In reference to motor unit diseases
How does the function of dystrophin change when normal in comparison to when its mutated
Week 2 - Motor Units
- Normal function - links actin cytoskeleton to extracellular matrix
- Gives mechanical support
- Allows membrane stabilisation during muscle contraction and relaxation
- Mutation causes loss of function
- Lack of mechanical support means increased mechanical stress during sliding of filaments, over time causing degeneration
In reference to motor unit diseases
What is dystrophin
Week 2 - Motor Units
- An X-linked muscle cell membrane associated protein
In reference to motor unit diseases
What treatments (if any) exist for Duchenne Muscular dystrophy
Week 2 - Motor Units
- No routine treatments
- palliative care (end of life care)
- Have been attempts to use antisense oligonucleotides
- Early clinical trials show some improvement in motor function
In reference to motor unit diseases
Outline Antisense treatments as a treatment for DMD
(DMD = Duchenne muscular dystrophy)
Week 2 - Motor Units
- Injected into patient muscle
- Binds to genomic DNA,
- Induce exon skipping in dystrophin gene
- Remove mutated exon
- Restore some normal dystrophin function
In reference to motor unit diseases
Outline how clinical trials have shown improvement in restoring motor funcion for DMD patients
(control group vs experimental group)
Week 2 - Motor Units
In control steroid group, there was very limited ability to run or walk
In group given antisense oligonucleotide, there was an increased velocity in ability to walk and run 10ms
