Myelinated and unmyelinated axons: how they work and what they do 1

Anatomy of a human nerve Connective tissue Axons contained in fascicles 2

Anatomy of a human nerve Fascicle in detail: wide range of axon sizes Diameters range from μm Some myelinated, some not 3

Relations between glial cells and axons 1. Myelinated axons CNS: each oligodendrocyte myelinates several axons PNS: each Schwann cell myelinates one axon Schwann cell spirals around axon 4

2. Mammalian unmyelinated axons Fundamental unit is the Remak bundle: one Schwann cell supporting several axons Relations between glial cells and axons 5

Faster conduction velocity for the same diameter or smaller diameter for a given conduction velocity Example: Frog nerve fibre: diameter 20 μm, myelinated Conduction velocity ~25 m/s at 20 °C Squid giant axon: diameter 1 mm, unmyelinated Conduction velocity ~25 m/s at 20 °C Takes up 2500 times more space! Why myelination? 6

Measuring conduction velocity in nerve Stimulating electrodes Recording electrodes Conduction distance d 7

Measuring conduction velocity in nerve Conduction time t 8

Measuring conduction velocity in nerve Conduction velocity v = d / t Conduction distance dConduction time t 9

Heterogeneous conduction velocities Conduction velocity heterogeneity is a consequence of: different axon diameters myelination or not Conduction velocity also relates to function... 10

Relating conduction velocity to function GroupCVDiameterFunction m/sμm SENSORY (afferent) Myelinated Aα Muscle spindle afferent Aβ Light touch sensation Aδ Sharp pain, strong heat, cold Unmyelinated C Dull pain, ache, itch, warmth, cold MOTOR (efferent) Myelinated Aα Muscle contraction Aγ Muscle spindle adjustment Unmyelinated C Sympathetic, parasympathetic 11

How does myelinated nerve conduct? Unmyelinated nerveMyelinated nerve Action potential is generated only at the nodes Conduction between nodes is instantaneous That’s why it is so fast 12

Saltatory conduction (textbook view) 13

But... how long is an action potential? Duration about ms Conduction velocity about 50 m/s (50 mm/ms) So length is about 50 x mm = mm Internodal length is about 1 mm So during an action potential about nodes are depolarised at any one time Not like this! 14

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 15

50 0 mV 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 16

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 17

Evidence for myelinated nerve conduction First dissect a single myelinated nerve fibre… (Schwarz, Reid & Bostock 1995) 18

Evidence for myelinated nerve conduction Tasaki & Takeuchi

Local circuits in myelinated nerve Huxley & Stämpfli 1949: Air gap blocks conduction Saline bridge restores conduction 20

How axons conduct: local circuit currents 21

50 0 mV Time (ms) Schwarz, Reid & Bostock 1995 Action potential in time and space Threshold Depolarisation Repolarisation 1. Time 22

Depolarisation Repolarisation Conduction direction Threshold Action potential in time and space 2. Space 23

Local circuit currents during the AP Na + in Depolarisation K + out Repolarisation Conduction Threshold ??? 24

Local circuit currents during the AP 25

Local circuit currents during the AP 26

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” Local circuit currents during the AP 27

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 along 28

Can we record local circuit currents ahead of the AP? Conduction 29

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? 30

Local circuit currents Stimulating electrodes Recording electrodes Frog sciatic nerve Recording setup: Recording electrodes can move along nerve 31

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

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 Hodgkin

Reading for today’s lecture: Nerve conduction and myelination Purves et al chapter 3 (page 49 onwards) Purves et al chapter 9 (pages ) Nicholls et al pages See also “Extra material on space constant” on website Next lecture Na + and K + channels Purves et al chapter 3 (up to page 48) and chapter 4 Nicholls et al chapter 6 pages and chapters 2-3 Kandel et al chapter 6