Peripheral Nerves (Week 1--Schweizer)

Question 1

Peripheral nerve

Answer 1

Contains many axons of diverse function and diameter, carrying both efferent motor and afferent sensory information

Some axons within peripheral nerve are myelinated by Schwann cells and others are not

Question 2

Epineurium

Answer 2

Ensheaths the peripheral nerve

Loose connective tissue composed of fibroblasts, mast cells, blood vessels and multiple layers of collagen

Gives tensile strength to nerves

Question 3

Perineurium

Answer 3

Encloses individual fascicles

Composed of concentric sheets of endothelial cells that are connected by tight junctions

Collagen between layers of endothelial cells

Tight sleeve is the blood-nerve barrier

Question 4

Endoneurium

Answer 4

Ensheaths each individual axon

Composed of collagen fibers, ECM and basal lamina adjacent to Schwann cells that enwrap individual axons

Question 5

“Layers” of peripheral nerve

Answer 5

Axons make up fascicles (bundles) which are grouped into nerves

Question 6

Are non-myelinated axons in PNS wrapped with Schwann cells?

Answer 6

No, they are not WRAPPED with Schwann cells, but they are still supported by Schwann cells!

Schwann cells surround non-myelinated axons, but do not wrap around many times

Question 7

How many Schwann cells per axon?

Answer 7

One Schwann cell can support many non-myelinated axons

Only one single Schwann cell wraps around one single axon for myelinated axons

Note: in CNS, one single oligodendrocyte can wrap many axons with a myelin layer

Question 8

Node of Ranvier

Answer 8

High concentration of Na+ channels to allow for AP propagation

Also surrounded by voltage gated K+ channels (helps with repolarization by letting K+ out); also astrocytes at node sop up K+

Question 9

What kind of axon conducts an impulse the fastest?

Answer 9

Large, myelinated

Ex: muscle spindle primary endings, golgi tendon organs, lower motor neurons are the largest

Question 10

How is axon diameter related to speed of conduction?

Answer 10

Increasing diameter increases speed of conduction by square root of diameter in non-myelinated axons

Increasing diameter increases speed of conduction linearly in myelinated axons

Question 11

Shorter internodal distances mean faster saltatory conduction, but why don’t we have nodes very close to one another?

Answer 11

Size of Schwann cells (specifically the nucleus) limits lower end (smallest possible) internodal distance for peripheral axons

Question 12

Which fibers are the fastest?

Answer 12

Large diameter, myelinated fibers carry proprioceptive information about skeletal muscles (A-fibers)

(note: what about muscle spindle, golgi tendon and lower motor neuron…these look biggest/myelinated…)

AP velocity can reach 200mph!

Question 13

Which fibers are the slowest?

Answer 13

Small diameter non-myelinated fibers carry mainly pain information (C fibers)

Question 14

Compound action potential (CAP)

Answer 14

Electrical activity generated when ensemble of axons in a nerve fire AP simultaneously

This only occurs in response to external stimulus delivered by a person! Does not occur during normal nerve activity, but has great diagnostic value

Several peaks visible because individual nerves within peripheral nerve fire APs that travel at distinct speeds, depending on myelination and fiber diameter

Question 15

Phases we are seeing in CAP wave form

Answer 15

1) Axon at rest so negative on inside
2) Axon depolarized so positive on inside at beginning
3) No voltage difference between recording electrodes because whole inside positive
4) Hyperpolarization?
5) Back to resting membrane potential

Question 16

How do you calculate the nerve conduction velocity (NCV)?

Answer 16

Test two stimulation sites, take the difference in latency, calculate NCV

Question 17

Sensory nerve action potential (SNAP)

Answer 17

Activity of all sensory fibers stimulated

No synapse between stimulation and recording sites

SNAPs much smaller than CAMPs (microvolts)

Question 18

Compound motor action potential (CAMP)

Answer 18

Measure of near simultaneous activation of many muscle fibers

Motor nerve stimulated, AP propagates to NMJ, triggers ACh release and postsynaptic AP in muscle is measured

Includes a synapse

In the millivolt range

Question 19

EMGs are more sensitive so why don’t we just use those?

Answer 19

EMGs require intramuscular electrodes and thus are more invasive

Question 20

What happens if you get local demyelination of a nerve?

Answer 20

Can get slowing or even block of AP propagation

Question 21

Why do you get slowing or block after demyelination?

Answer 21

Current flowing through few Na+ channels at original Node of Ranvier not enough to charge large membrane capacitance of non-myelinated segment

Also, charge lost via dispersion through axon where no more myelination?

Question 22

How can you repair a demyelinated nerve?

Answer 22

1) Remyelinate
2) Insert additional Na+ channels in demyelinated segments

Question 23

What happens to the neuron after injury to the axon?

Answer 23

Axon distal to injury site undergoes active process of degeneration (Wallerian degeneration)

Activation of degradative enzymes and “balling up” of myelin sheets into “myelin ovoids”

Area gets infiltrated by macrophages

Proximal cell body undergoes “chromolysis” (RNA containing structures such as polyribosomes and rER disappearing) and Nissl bodies disappear; cell body can also undergo apoptosis

If cell body does not die: proximal axonal stump starts sprouting shortly after injury and distal Schwann cells proliferate to form a tube (Bunger’s band) that helps guide sprouting axon in direction of lost axon; if crush injury, basal lamina and perineum help guide growing axon

If axon reaches its target, eventually will be re-myelinated

If reconnection fails, target atrophies over time

Question 24

Why is a crush injury better than a cut nerve?

Answer 24

Because you’d still have basal lamina and perineurium intact, which can help guide newly growing axon

Question 25

What happens to the CAP if you have demyelination?

Answer 25

CAP is slowed

Since demyelination not uniform across different axons, individual APs are slowed to a different extent which leads to temporal dispersion –> reduction in amplitude of CAP

When responses arrive at recording electrode together, get big wave; when responses arrive at different times, get phase cancellation

Question 26

What is one main function of myelin?

Answer 26

1) Reduces membrane capacitance
2) Lowers lateral “leak” of current since there are hardly any channels in internode

Question 27

CAP in normal vs. demyelinated nerve

Answer 27

CAP in normal nerve: CAP in different parts all arrive at muscle at same time; productive summation, large amplitude, narrow waveform

CAP in demyelinated nerve: some CAP are slowed at demyelinated site; cancellation, small amplitude, temporal dispersion

Question 28

CMAP in disease

Answer 28

Axonal degeneration: get smaller signal both proximal and distal to the injury

Local demyelination: get low signal proximal to injury and normal signal distal to injury

Conduction block: get low signal proximal to injury and normal signal distal to injury (similar to local demyelination)