Neuromotor L1 Flashcards
1
Q
What does the neuromotor system?
A
2
Q
What are upper MNs (Betz cells motor cortex)?
A
Anterior to central sulcus
Layer 5 cells
Project to spinal cord
3
Q
What are Acetylcholine receptors?
A
Open for positive ions to flow in –> generate muscle contraction (AP)
4
Q
What are alpha-motor neurons?
A
Cell body + spindly dendrites
5
Q
What does the overview of neuromotor system?
A
6
Q
____ motor neurons are the final output neuron.
A
Alpha
7
Q
What are 4 characteristics of motor neurons which are the final output neuron?
A
- Biggest neuron is ventral horn
- Can inhibit it –> hyperpolarise
- Can excite it –> depolarise
- Can change firing output
8
Q
What are the 2 types of motor neurons in the ventral horn of the spinal cord?
A
- Alpha
- Gamma
9
Q
How can you introduce Learning and memory, voluntary and modifying movement?
A
- Learnt after birth
- Eg. pre-mature babies –> poor visual tracking, fine motor skills take a while get developed
10
Q
What are 11 functions of the skeletal muscle (effector organ)?
A
- Movement (includes Vocalization- Laryneal muscles and Respiration- Diaphragm)
- Maintains Posture- Brainstem nuclei
- Stabilizes Joints
- Generates Heat
- Skinner person feels cold more (hard to generate heat)
- Bigger person can generate more heat (more mitochondria to muscles, muscles are hypertrophied
- Helps with peripheral (Venous return)
- Lymphatic drainage- Removing ECF and infections to lymphatic nodes
- One way valves –> muscles contract to pump
- Vision
- Reproduction
- Digestion
- Excretion
11
Q
What are the 4 levels of organisation in the structure of muscle?
A
- Whole muscle (organ)
- Muscle fibre (multi-nucleated Muscle cell - composed of many myofibrils
- Cytoskeletal components of a Myofibrils
- Protein components of myofibrils myosin (thick filaments) actin (Thin filaments), troponin Tropomyosin.
12
Q
What are the 4 features of the neuromuscular synapse (junction)?
A
- Biggest chemical Synapse in the body (25 um)
- Excitable synapse
- Simple
- Can undergo Re-innervation if damaged (close by)
13
Q
What are ligand binding channels?
A
- Ach allows channels to open up
- Positive ions flow through/in
- Membrane potential depolarises
- One voltage gated Na+ channels
- Membrane potential rises even further
- Get to threshold Muscle contraction
14
Q
What type of contractions do slow twitch fibres cause?
A
Graded muscle contractions
15
Q
What type of contractions do fast twitch fibres cause?
A
If doesn’t get to threshold wont get muscle contraction
16
Q
When Ach (neurotransmitter) is released and binds, what happens?
A
If it doesn’t get cleaned up or destroyed, it can go into the Na+ channels and keep activating it
Eg. drugs that inhibition of Ach breakdown
17
Q
Why do you need to to break down Ach?
A
- Need to be able to recycle it –> break down and pumped out again
- Limiting action of the neurotransmitter
- In terms glutamate and GABA –> Remove them from synaptic gap
- Glial cells which have pumps
- If no glial cells = excitotoxicity (glutamate can cause increase Ca++ and neurons can dye)
- Need to regulate the life of the trransmitter before pre and post synapse
18
Q
What does it look like when Alpha motor neuron connect with skeletal muscle to from the neuromuscular synapse?
A
19
Q
What are 9 steps of the ___?
A
- Action potential arrives at motor nerve terminal
- AP triggers the opening Of VGCCs (P/Q Type Next to Active zones) entry of Ca2+
- Ca2+ dependant release by exocytosis Of acetylcholine (ACh) from synaptic vesicles
- ACh traverses the synaptic cleft To bind to its receptor a ligand gated Ion channel (AChRs).
- This binding bring about the opening of this ion channel to cause a large movement of Na+ in and a small movement of K+ out of the Muscle cell.
- The result is an endplate Potential – (Depolarization). This sets up a local Current flow between the depolarized Post-synaptic membrane and adjacent membrane of muscle.
- This local current flow opens voltage gated Na+ channels in the adjacent memb.
- The resulting entry of Na+ causes the Resting membrane potential to rise from ~ -70 mV to -60mV . This triggers the generation of a muscle action potential
- ACh is subsequently destroyed by Acetylcholinesterase an enzyme located in the synaptic cleft,
20
Q
What happens when Muscle Action Potential is generated that in turn will trigger Muscle Contraction?
A
21
Q
What are the 8 steps of the Excitation Contraction Coupling of Skeletal Muscle?
A
- Alpha MN Action Potential (AP) to Motor Nerve terminal
- Ca++ enters nerve terminal -> synaptic vesicles to release Acetylcholine.
- Acetylcholine binds to receptors sets up a Muscle AP
- Muscle AP is propagated across the muscle surface and down the T tubules
- Muscle AP triggers Ca++ release from sarcoplasmic reticulum
- Ca++ in the cytoplasm is free to interact with troponin on actin filaments. Set in motion the cross - bridge actin myosin cross bridge cycle (sliding filiament) to bring about muscle contraction - powered by ATP.
- Ca++ actively taken back up by sarcoplasmic reticulum by carrier Ca++ ATPase pump in sarcoplasmic reticulum, when local AP is no longer present
- Contraction ends actin slides back to original resting position.
22
Q
What steps out of 8 is synaptic transmission, (first 3 points( is very fast but observation of muscle twitch takes longer (excitation-contraction coupling and mechanics)?
A
- Alpha MN Action Potential (AP) to Motor Nerve terminal
- Ca++ enters nerve terminal -> synaptic vesicles to release Acetylcholine.
- Acetylcholine binds to receptors sets up a Muscle AP
23
Q
Muscle action potentials last for only____ to ____ ms, whereas the muscle contraction that results can last about ____ ms. The time delay between stimulation and contraction is called the ______.
A
1 to 2; 50; latent period frequency of Action potentials
24
Q
What are rate modulation?
A
Motor nerve actions of Skeletal muscle, from Muscle Action Potentials to Muscle Fiber twitch
25
What is increasing AP frequency?
AP frequency – Twitch Summation-Tetanus
26
What are 3 characteristics of rate modulation?
1. Increasing the firing rate of motor units – each Motor Units increases its force contribution as frequency increases
2. has as its basis twitch summation to tetanic contractions
3. muscle contraction is smooth because motor units are activated asynchronously
27
If one moto neuron Small control --\> more motor units (need to make more connections which have small control) Large force generated Small muscle = small motor unit (face, hands, feet) Large muscle = large motor uni (trunk, arm, leg)
a
28
What are 4 diseases of the neuromuscular synapse (junction)?
1. Myasthenia Gravis
2. Lambert-Eaton Syndrome
3. Spinal Muscular Atrophy (SMA)
4. Motor Neuron Disease (Upper and Lower MNs)
29
What is Myasthenia Gravis? WON'T BE TESTED
causes the drop in the number of post-synaptic AChRs to such a level that causes muscle weakness. caused by genetic mutations to molecules that bring about high numbers of AChRs, can also be caused by auto-antibodies to AChRs which trigger endocytosis of AChRs
30
What is Lambert-Eaton Syndrome? WON'T BE TESTED
auto immune self antibodies to the presynaptic voltage gated calcium channels (probably P/Q type calcium channel) poor pre-synaptic release of neurotransmitter - leads to neuromuscular block
31
What is Spinal Muscular Atrophy (SMA)? WON'T BE TESTED
an autosomal recessive disease caused by a genetic defect in the SMN1 gene, which encodes SMN, a protein widely expressed in all eukaryotic cells. SMN1 is apparently selectively necessary for survival of motor neurons (Lower Motor Neuron Disease. Defects 1st seen at the NMJ
32
What are 2 types of Motor Neuron Disease? WON'T BE TESTED
1. Upper
2. Lower MNs
33
What is the common phentotype- muscle weakness in the 4 disease of neuromuscular synapse (junction)?
34
What is the difference/similarity between Lambert-Eaton Syndrome VS Myasthenia Gravis?
* Same phenotype = muscle weakness
* Either pre or post Eg. botox = paralyses muscles
* Kill pre-synaptic release of neurotransmitters
* Chronic denervation = fibre type grouping
35
What is chronic denervation?
fibre type grouping
36
What is disease of the target organ - skeletal muscle = Muscular Dystrophies?
Caused by genetic mutations to dystrophnin and/or to molecules that associate with dystrophnin (directly and/or indirectly) - Congenital Muscular Dystrophy
X-linked --\> when go eccentric movements (gets stretched) --\> gets activated --\> molecular connectors are broken (muscle membrane) --\> shearing of muscles --\> muscle damage
37
What is the Pathogenesis in Duchenne Muscular Dystrophy?
38
Regeneration/dennervation cycle = but only a limited amount of time = start to loss muscle mass as already reached the limit for regeneration? What happens?
* Inflammatory response --\> inflammatory mediated cell death of muscle --\> becomes fat
* High fat content
39
How does the Neuromotor System grade the force of muscle contraction ?
40
Small motor units fine control but \_\_\_\_(stronger/weaker) muscle Contraction. Large Motor Units – _____ (larger/smaller) muscle contraction
weaker; larger
41
What does Alpha motor neuron connect with skeletal muscle to from the neuromuscular synapse look like?
42
Name a common skeletal muscle disease
Muscle dystrophy
43
Define a motor motor unit?
One neuron and a set number of fibres that it connects to
44
Are Motor units composed of one muscle fiber type? Why?
Yes --\> determined by innervation pattern of the motor nerve --\> Nerve will dictate fibre type
45
Motor neuron in the spinal cord (Alpha motor neurones because they innervate _____ (extrafusal/infrafusal) muscle fibres because _____ (extrafusal/infrafusal) l muscle fibres are present in muscle spindles which provide sensory feedback with changes in muscle length)
extrafusal; intrafusal
46
Motor nerve terminal has volatage gated ____ channels. Very close to nerve terminal membrane (important). Ca++ can be toxic --\> highly buffered --\> close to site of action Vesicle fused with pre-synaptic membrane = ____ release
Ca++; Ach
47
Ach travels pass the synaptic cleft and binds to ______ (ligand ion channels --\> binds to them and physically opens channels). This happens at the region below the motor \_\_\_\_\_\_.
Ach receptors; nerve terminal
48
What is Henneman's Size Principal?
For a given synaptic input
Motor neurons with the smallest cell bodies are activated 1st & large motor neurons are activated last.
49
Increase frequency of action potentials = \_\_\_\_\_(more/less) transmitter = more _____ (pre/post) synaptic receptors = more ions to flow in = reach threshold = \_\_\_\_\_(graded /abrupt)
more; post; graded
50
Different size MNs innervate different _____ within a muscle
fiber types
51
Small MNs to Slow Type muscle fibers – type 1 Myosin (smallest tension but not fatigable) – these Small MNs have small axon diameter and have ____ (small/large) motor units
small
52
Medium MNs to Fast Fatigable Resistant type muscle fibers IIA– these MNs have larger axons and \_\_\_\_(small/larger) motor units
larger
53
Large MNs to Fast Fatigable type muscle fibers IIX (IIB) – these MNs have large axons and \_\_\_\_\_(large/small) Motor units
large
54
Motor Units are recruited from the \_\_\_\_\_(largest/smallest) to the \_\_\_\_\_(largest/smallest)
smallest; largest
55
What is the motor unit recruitment?
Small MNs – Small Motor units (small total muscle tension) then with increasing synaptic current input
Large MNs are activated – Large + Small Motor units are recuited – increases in Whole muscle tension.
56
Increase drive --\> generate action potentials --\> overall force is greater. What does the Size principle look like?
a
57
What are the various properties of different fibre types?
58
What are the 3 fibre types within motor units?
* Type 1= slow oxidative
* Type IIa= fast oxidative
* Type IIx= fast glycolytic
59
What is type 1 fibre type?
Slow Oxidative (Not by glycolysis)
type 1 MHC, slow contraction, Low myosin ATPase activity. Fatigue resistant, high oxidative Phosp capacity, many mitochondria, low enzymes for anaerobic glycolysis
60
What is type IIa fibre type?
Fast Oxidative
type IIa MHC, fast contraction, Resistence Fatigue Intermediate, Oxidative Phosphorylation High, enzymes for anaerobic glycolysis Intermediate, many mitochondria, high myoglobin content, red fiber, glycogen content intermediate. Many capillaries
61
What is type IIb fibre type?
Fast Glycolytic
Type IIx Myosin. Fast contraction, High myosin ATPase activity. Fatigue easily, low oxidative Phosp capacity, few mitochondria, high enzymes for anaerobic glycolysis, high glycogen content, low myoglobin content, white fiber. Few capillaries
62
Under sustained contraction total muscle tension declines over time – despite increased effort to maintain maximal muscle contraction – WHY?
Due to fatigue
Motor neurons (type Iix) drops out, not synaptic transmission--\> biochemical exhaustion of type IIx fibres Eg. train for endurance and not loss motor units --\> train body to have more Type IIa fibres
63
Chronic denervation re-innervation events lead to type _____ fiber predominance. This is best seen in _____ – where _____ Motor neurons die first Also seen in ageing where _____ motor neuron may be more venerable with age.
1; MND; fast; fast
64
What is the plan for chronic denervation?
reinnervation of muscle can lead to fiber type grouping Typically fiber type I.
65
Larger motor neurons have \_\_\_\_\_(higher/lower) metabolic loads --\> more _____ to stress over the whole life of the organism Eg. in motor neuron diseases --\> first to die are the type II fibres (fast twitch), type I last longer
higher; vulnerable
66
What does 2 motor unit expansion?
67
Chronic denervation re-innervation is best seen in neurological conditions. When looking at ageing --\> in geriatrics (late 50s, 60s, and 70s). What does it look like?
* Can measure motor neuron expansion
* Most of the time don’t see a change in muscle strength --\> will promote the maintenance of muscle strength ○ As you age --.\>Start to muscle atrophy
* Type Iix are vulnerable
68
What are 2 observations of Fibre type conversion occurring quickly in pathology that is chronic?
1. Muscle weakness
2. Muscle atrophy
69
What is Motor nerve activity drive: Myosin isotype expression which determines muscle twitch (fast or slow)?
70
Took a small motor neuron and forced it to innervate a ____ (large/small) motor neuron Took a fast motor neuron and forced it to innervate a \_\_\_\_(fast/slow) motor neuron
large; slow
71
When denervate a muscle or an embryonic muscle that is just developing,they have embryonic fast myosin. What happens?
NS gets built --\> slow and fast firing properties --\> start to differentiate
72
SUMMARY To drive slow fibre myosin type --\> an acted program Go back to a fast type myosin --\> Default program
Eg. if denervated slow type muscle --\> degrade in slow and becomes a fast If it it re-innervated by slow motor neuron again --\> switch back to a slow
73
What are the 3 levels of input control motor neurons output?
1. Input of afferent (sensory) – reflexes
2. Primary motor cortex (direct - Hierarchical)
3. Multi-neuronal motor system (indirect - parallel)
74
What are feedback sensory receptors?
* Feedback sensory receptors
* direct connections onto motor neurons (eg. knee jerk --\> monosynaptic)
* Modify that reflex by upper motor control (many inputs into control --\> polysynaptic)
75
What are joint receptors?
information on spatial position of Joints
76
What are muscle spindles?
* Intrafusal muscle fibers 2 types (chain and bag) receive motor innervation
* Via Gamma Motor Neurons (small) -which maintain the sensitivity of the spindle during muscle contraction.
* Muscle spindles activated by stretch e.g. tap the patella tendon will cause the muscle spindle to lengthen and thus activate it.
77
What is a nuclear bag?
muscle length and velocity
78
What is the nuclear chain?
muscle length
79
Muscle spindles (intrafusal fibres) are encapsulated with the \_\_\_\_\_. What are 2 characteristics of muscle spindles?
muscle belly
* Central neutrons that will go back to spinal cord
* Have a motor innervation
* Extrafusal muscle fibres --\> innervated by alpha motor neurons (eg. NMJ)
80
What are the muscle spindle afferents and efferents?
81
What are mechanoreceptors?
* What generates the action potentials at the central nerve endings
* When they are activated --\> will change the membrane potential --\> generate an AP
82
Gamma MNs Act to on _____ (intra-fusal muscle fibers) to keep in register with the Changing length Of _____ muscle Fibers – g MNs Maintain muscle Spindle sensitivity During muscle contact
muscle Spindles; extra-fusal
83
Sensory information is going to \_\_\_\_\_\_.
spinal cord
84
When extrafusal muscles are contracting, _____ also have to contract. What are 4 characteristics?
muscle spindles
Must have its own motor innervation to match the extrafusal activity = gamma motor neuron
* When it does --\> see information coming back to the spinal cord in the change in rate of length OR the new resting length
* Only works because it is contracting in registration with the muscle fibres
* Are quite small and sit around the motor pool
85
What are 4 characteristics of Golgi Tendon Organs?
1. Located in the tendinous insertions of muscle
2. Encapsulated structure with afferent type Ib nerve endings
3. intertwined amongst collagen fibers
4. Detects changes in Muscle tension
86
Golgi tendon organs are activated by increases in muscle tension and thus measure the degree of tension/load that the muscle is under. E.g. as the muscle (extra fusal fibers) contract it is trying to shorten this puts Increased stretch-tension on the tendons at each end of the muscle as these tendons dig into the bone. This causes the collagen fibers to close up and pinch in on the inter winding sensory nerve endings. What does that look like?
87
What are some characteristics of joint receptors?
* Sensory Nerve Endings in the Joint Capsule - Information about
* Joint Position Eg. knee (synovial and caapsular)
* Free nerve endings in membranes which detect joint position/joint degrees
* Proprioceptive input (from peripheries)
* Free nerve endings
* Muscle spindles
* Golgi tendon organs
88
What is the role of the spinal cord in motor activity?
* Reflex Movements - solely by spinal cord Motor Neuron organisation of Spinal cord a MNs - ventral horn g MNs - ventral horn Motor Columns within the spinal cord. LMC (brown) – later motor Column (Cervical-Brachial = extra motor neurons for head neck, fore limb; and Lumbar – lateral motor column – extra Motoneurons for lower limb. MMC (blue) – medial motor column – motoneurons for axial muscles
89
What are 4 characteristics of inter-neurons (INS)- spinal cord?
1. connection between afferents inputs
2. \* connections between gps of MNs same side (ipsilateral) opposite side (contralateral) different segmental levels
3. function to co-ordinate the activities of muscle groups
4. their afferent inputs
90
What do Reflexes of the limbs are mediated by spinal reflex pathways and long loop pathways that involve the motor cortex look like?
91
What does an example of inter-neuronal circuits?
92
What are spinal cord reflexes?
* MNs (a & g) + Afferents + INs = Spinal Reflex components
* Myostatic Reflex e.g. of -ve feedback (muscle pulled - pulls back)
* mono-synaptic reflex - very quick.
* It helps maintain muscle tone
* It can also be used to demonstrate reciprocal inhibition! (e.g. of Gating)
93
What are the 4 steps of the Monosynaptic reflex (this is activated 1st)?
1. It the patella tendon
2. Activates muscle spindle --\> not golgi tendon (as change length)
3. AP from peripheral into spinal cord
4. Back down to the same muscle
94
What are the 2 steps of the What are the 4 steps of the Monosynaptic reflex (this is activated 1st)?
1. When the AP from periphery goes into spinal cord back to same muscle, a copy of that information goes into an inhibitory motor neuron to the antagonist muscle (flexors)
2. Closed the gate on that neuron (antagonist muscle) for a period of time --\> non-responsive
95
What does the Crossed Extensor coupled with Withdrawal Reflex look like?
* Locomotion (walking) Avoiding injury (protective)
* Polysynaptic Activation and Inhibition via Ins
* Both sides of Body (Ipsilateral & Contralateral)
* Forms the basis of locomotor circuits for alternating flexion and extension.
* Walking Will have these types of circuits in spinal cord --\> stimulated by the one input
96
What does an example of inter-neuronal circuits look like?
97
What happens in Myoclonus – the loss of inhibitory glycinegic transmission in the spinal cord?
Limbs before very stiff and shakes a lot
98
What does the half-center model for Rhythmic Activity attempt to explain?
99
What does Interneurons for the half center neural network within the spinal cord next to between ventral and dorsal horns look like?
100
When you look at the ____ neurons, the last neurons in the chain to the muscles --\> some action potentials are coming and some are out of phase
effector
101
Interneurons are really important for hooking up or connecting different groups of motor neurons to muscles Inhibitory: silence info Excitatory: pass info
a
102
What does Half centre model of Rhythmic Activity (basis of a locomotor generators) look like?
103
What are 10 characteristics of out-patients in SCIPA Full-on Phase III randomised controlled trial?
1. Whole body exercise
2. Not just about walking
3. Reverse bone &muscle loss
4. Neurological recovery
5. Spasticity
6. Cardiovascular fitness
7. Urinary output
8. Blood pressure
9. Core stability
10. Reduce secondary complications
104
What are upper motor neuron lesion?
Loss of motor neuron to the muscle --\> key feature: atrophy (muscles paralysed)
105
What are lower motor neuron lesion?
If can maintain some sort of therapy to activate spinal cord circuit = can maintain muscle mass
* Some reflexes increased because no ascending inputs to control output
