Myelinated and unmyelinated axons:how they work and what they do

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Anatomy of a human nerve

Connective tissue

Axons contained in fascicles

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Anatomy of a human nerve

Fascicle in detail: wide range of axon sizes•Diameters range from 1 - 20 μm•Some myelinated, some not 3

Relations between glial cells and axons1. Myelinated axons

CNS: each oligodendrocyte myelinates several axonsPNS: each Schwann cell myelinates one axon

Schwann cell spirals around axon

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2. Mammalian unmyelinated axons

Fundamental unit is the Remak bundle: one Schwann cell supporting several axons

Relations between glial cells and axons

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Faster conduction velocity for the same diameterorsmaller diameter for a given conduction velocity

Example:Frog nerve fibre: diameter 20 μm, myelinatedConduction velocity ~25 m/s at 20 °CSquid giant axon: diameter 1 mm, unmyelinatedConduction velocity ~25 m/s at 20 °CTakes up 2500 times more space!

Why myelination?

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Measuring conduction velocity in nerve

Stimulating electrodes

Recording electrodes

Conduction distance d

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Measuring conduction velocity in nerve

Conduction time t 8

Measuring conduction velocity in nerve

Conduction velocity v = d / t

Conduction distance d Conduction time t

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Heterogeneous conduction velocities

Conduction velocity heterogeneity is a consequence of:•different axon diameters•myelination or notConduction velocity also relates to function... 10

Relating conduction velocity to function

Group CV Diameter Functionm/s μm

SENSORY (afferent)MyelinatedAα 70-120 12-20 Muscle spindle afferentAβ 35-70 6-12 Light touch sensationAδ 5-30 1-6 Sharp pain, strong heat, cold

UnmyelinatedC 0.5-2 0.5-1 Dull pain, ache, itch, warmth,

cold

MOTOR (efferent)MyelinatedAα 70-120 12-20 Muscle contractionAγ 12-48 2-8 Muscle spindle adjustment

UnmyelinatedC 0.5-2 0.5-1 Sympathetic, parasympathetic

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How does myelinated nerve conduct?

Unmyelinated nerve Myelinated nerve

•Action potential is generated only at the nodes•Conduction between nodes is instantaneous•That’s why it is so fast

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Saltatory conduction (textbook view)

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But... how long is an action potential?

•Duration about 0.5-0.8 ms

•Conduction velocity about 50 m/s (50 mm/ms)

•So length is about 50 x 0.5-0.8 mm = 25-40 mm

•Internodal length is about 1 mm

•So during an action potential about 25-40 nodes are depolarised at any one time

•Not like this!

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What determines conduction velocity?•Current through the membrane can be measured from the outside (because currents flow in a loop)

Huxley & Stämpfli 1949

•Conduction within each internode is instantaneous

•Brief delay (~20 μs) at each node

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50

0

mV

-50

-100

0 1 2 3 4 msec

Schwarz, Reid & Bostock 1995

What determines conduction velocity?•Nodal delay in a real recording from a human nerve fibre

•The delay is the time taken to reach threshold (the subthreshold depolarisation)

•This is the time it takes to charge the membrane capacitance

Threshold

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Evidence for the importance of the node

How do we know action potentials are generated at the node?

•Threshold is low at node, infinitely high in internode•Cooling slows conduction if applied at the node, not in internode•Blockers (e.g. local anaesthetics) applied at node are effective•Blockers applied in internode have no effect

•Most importantly: inward current during an action potential appears only at the node, not in the internode(Tasaki & Takeuchi 1942, Huxley & Stämpfli 1949)•Inward current is the sign of active membrane

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Evidence for myelinated nerve conduction

First dissect a single myelinated nerve fibre…

(Schwarz, Reid & Bostock 1995)18

Evidence for myelinated nerve conductionTasaki & Takeuchi 1942

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Local circuits in myelinated nerve

Huxley & Stämpfli 1949:

Air gap blocks conductionSaline bridge restores conduction

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How axons conduct: local circuit currents

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50

0

mV

-50

-100

0 1 2 3 4 Time (ms)

Schwarz, Reid & Bostock 1995

Action potential in time and space

Threshold

Depolarisation

Repolarisation

1. Time

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Depolarisation

Repolarisation

Conduction direction

Threshold

Action potential in time and space2. Space

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Local circuit currents during the AP

Na+ in

Depolarisation

K+ out

Repolarisation

Conduction

Threshold

???

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Local circuit currents during the AP

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Local circuit currents during the AP

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What do local circuit currents consist of?

- Currents in aqueous solutions consist of ions moving- Movement along the axon is limited but ions “bump into” neighbouring ions to produce the appearance of a flow from one point to another- Like “Newton’s cradle”

http://commons.wikimedia.org/wiki/File:Newtons_cradle_animation_book.gif

Local circuit currents during the AP

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What happens ahead of the AP?

Na+ ions entering during AP

K+ ions leaving during repolarisation

+ + +

– – –

...but what’s going on here?

Charge buildup across membrane…positive inside

Na+ and K+ ions “bumping” each

other along28

Can we record local circuit currents ahead of the AP?

Conduction

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Local circuit currents:how can we record them?

•First need to block the AP

•Hodgkin (1937): first to record local circuit currents in blocked nerve

•What did he do?

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Local circuit currents

Stimulating electrodes

Recording electrodes

Frog sciatic nerve

•Recording setup:

Recording electrodes can move along nerve

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Action potential arriving at block

1.4 mm after block

2.5 mm after block

4.1 mm after block

5.5 mm after block

8.3 mm after block

•Here’s what Hodgkin recorded:

Local circuit currents

Hodgkin 1937

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•Plotting amplitude against distance from block:

Exponential curve

•Falls off with distance like a graded (local)potential, like synaptic potential in lecture 1•Follows an exponential curve

Local circuit currents

Why use action

potentials?

•Without action potentials, voltage falls off quickly with distance

•This is OK in a short interneurone

•Over longer distances we need a digital code

Hodgkin 1937

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Reading for today’s lecture:

Nerve conduction and myelination•Purves et al chapter 3 (page 49 onwards)•Purves et al chapter 9 (pages 189-194)

•Nicholls et al pages 121-126See also

•“Extra material on space constant” on website

Next lectureNa+ and K+ channels

•Purves et al chapter 3 (up to page 48) and chapter 4•Nicholls et al chapter 6 pages 94-102 and chapters 2-3

•Kandel et al chapter 6