Motor Units Flashcards
motor units, diseases of the motor unit
What is the largest cell in the human body?
The human ovum
It can reach up to about 0.12 millimeters in diameter.
What is the diameter range of a motor neuron’s cell body?
0.04 to 0.1 millimeters
This is just the cell body diameter.
How long can the axon of a motor neuron be?
Up to a meter in length
Example: the motor neuron that innovates a muscle in the toe.
Where do upper motor neurons originate?
Motor cortex and premotor cortex
where do upper MN axons extend down to
brain stem and spinal cord
Where are the cell bodies of lower motor neurons located?
ventral horn of spinal cord (and some in cranial nerve nuclei in brain stem)
where do lower MN in the spinal cord extend down to
to skeletal muscle
what neurotransmitter do upper motor neurons use
glutamate
- glutamatergic transmission
what are all upper motor neurons considered
pyramidal cells
corticospinal tract what is it and where
- one of the many pathways UMNs use
- UMNs from cortex to LMNs in ventral horn of spinal cord
function of corticospinal tract
fine voluntary motor control of the limbs and voluntary body posture adjustments
What neurotransmitter do lower motor neurons use?
Acetylcholine
- cholinergic transmission
what are LMNs like
large neurons with extensive dendritic trees
what are the cell bodies of LMNs in ventral horn of the spinal cord
convergence of inputs from
a) sensory fibres
b) interneurons
c) descending pathways
What are motor neuron pools?
groups of motor neurons that supply an individual muscle
e.g. bicep MN pool
how LMNs are organised
how are motor neuron pools arranged
- longitudinal columns
What is the proximal distal rule in motor neuron organization?
Medial motor neuron pools innervate axial and proximal muscles (neck/shoulder)
lateral pools innervate distal muscles (hand, wrist, fingers)
What is a motor unit?
A motor neuron and the skeletal muscle fibers it innervates.
what do the properties of a MU depend on
- neuron
- muscle elements
what does the CNS control
muscle units NOT single muscle fibres (which are contained within MUs)
What factors influence the strength of a muscle contraction?
- frequency of action potentials/ firing rate of MUs
- recruitment of motor units
What is the size principle in motor neuron recruitment?
Small motor neurons are always activated before large motor neurons
Who first described the size principle?
Professor Heneman
why are small MNs recruited first ?
small SA cell bodies therefore:
- high density of synaptic inputs
- high electrical input resistance
EPSP and why SMNs recruited first
more likely to reach threshold to be activated
- larger EPSPs therefore more likely to fire AP
EPSP = synaptic current x input resistance
What is the main advantage of the size principle?
Allows for graded muscle contraction depending on force needed
e.g. fine movements only need small increments of force
- non-fatigable fibres used for most tasks and fatigable used sparingly
what does muscle force depend on
the MN firing rate and the total number and type of activated MU (recruited)
What are the two main types of lower motor neurons?
Alpha and gamma motor neurons
What do alpha motor neurons supply?
all lower motor neurons
Extrafusal muscle fibers
- large soma, large myelinated axons, fast
- control muscle force generation for voluntary movements
What do gamma motor neurons supply?
LMNs
Intrafusal muscle fibers (muscle spindles)
- smaller soma, smaller slower myelinated axons
- control muscle spindle responsiveness
What type of muscle fibers do small alpha motor neurons innervate?
- Type S MUS
- Type I muscle fibers
- weak, sustained contraction e.g. posture
what type of muscle fibres do intermediate alpha motor neurons innervate?
- type FR muS
- Type IIA muscle fibres
- moderate contractions e.g. running
What type of muscle fibers do large alpha motor neurons innervate?
- Type FF MUs
- type Type IIB muscle fibers
- powerful, phasic contractions e.g jumping (lest used)
motor neuron disease
- dysfunction of motor neuron cell body
What condition is characterized by defects in the cell body of the motor neuron?
Motor neuron disease or amyotrophic lateral sclerosis (ALS)
What are peripheral neuropathies?
Dysfunction of the axons and cells
What are neuromuscular diseases?
Defects in the synapse (neuromuscular junction)
What are myopathies?
Defects in the muscle fibers themselves
What is Guillain-Barré syndrome ?
A rapid onset muscle weakness caused by the immune system damaging the myelin of axons in the peripheral nervous system
-rapid and progressice, immune mediated peripheral neuropathy
What are the common symptoms of Guillain-Barré syndrome?
Numbness, tingling, pain in distal limbs, ascending weakness, facial weakness, respiratory failure, paralysis
Symptoms can lead to complete paralysis in severe cases.
What is the incidence rate of Guillain-Barré syndrome?
1 to 2 new cases per 100,000 per year
It is a rare disease.
What is the typical recovery rate for Guillain-Barré syndrome?
80% of patients will make a full recovery
15% left with disability
Recovery is generally slower in older individuals.
What causes Guillain-Barré syndrome?
Most commonly caused by bacterial or viral infections
- B cells start producing antibodies that target myelin and damage it and reduce conduction capacity of motor neuron
Examples include gastroenteritis, Epstein-Barr virus, Zika virus, and COVID-19.
How is Guillain-Barré syndrome diagnosed?
By measuring immune cell proteins in cerebrospinal fluid and nerve conduction tests
GBS treatment
- intravenous immunoglobulins
- plasma exchange to remove antibodies
- supportive care and rehabilitation
What is myasthenia gravis?
A neuromuscular junction disease
- affects transmission of signal at NMJ
- characterized by serious muscle weakness due to antibodies targeting acetylcholine receptors
The name is derived from Greek.
What is the primary mechanism of myasthenia gravis?
- autoimmune
- Antibodies produced block acetylcholine receptors, preventing muscle contraction
This leads to muscle fatigue, particularly in cranial muscles.
congenital MG
- rarer
- transfer of AChR antibodies across placenta
- transient
Inherited MG
- rarer
- mutations affecting ACh production and signalling in genes
What is a key diagnostic clue for myasthenia gravis?
- abnormal muscle fatigue due to prolonged contraction of cranial muscles
- No signs of denervation
This differentiates it from other neuromuscular disorders.
how to treat MG
- inhibition of ACh esterase
- prevent ACh degradation and can reverse symptoms
What is Duchenne muscular dystrophy (DMD)?
- a myopathy
- progressive skeletal muscle degeneration and weakness - - caused by a mutation in the dystrophin gene (X-linked recessive)(mostly boys)
- awkward walking before age 5
It is X-linked recessive and primarily affects boys.
What is Gowers sign?
A classical sign of Duchenne muscular dystrophy where a patient uses their hands to push against their legs to stand up
It indicates muscle weakness.
What is the median life expectancy for patients with Duchenne muscular dystrophy?
22 years
What is the function of dystrophin?
- muscle cell membrane associated protein
- links actin to the extracellular matrix in muscle cells and provides support and stabilization during muscle contraction and relaxation
It provides mechanical support during contraction and relaxation.
what does mutant dystrophin do to muscle fibres
causes them to undergo mechanical stress and susceptible to damage
What is the current treatment approach for Duchenne muscular dystrophy?
There are no routine treatments; most patients receive palliative care
Some promising clinical trials utilize antisense oligonucleotide technology.
what is antisense oligonucleotides
- removes mutated axon and restored some normal dystrophin function
- early clinical trials show some improvement in motor function
What is Viltolarsum?
An antisense oligonucleotide used in clinical trials for treating Duchenne muscular dystrophy
It targets mutated sequences in the dystrophin gene to restore some function.
What was the outcome of the clinical trial involving Viltolarsum?
Patients showed significant improvement in running speed over a 10-meter stretch
The improvement was maintained for up to 25 weeks.
