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R Cheung MSc Bioelectronics: PGEE11106 1 Neurons Pyramidal neurons in mouse cerebral cortex expressing green fluorescent protein. The red staining indicates GABAergic interneurons. MBL, Woods Hole

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Page 1: Neurons - University of Edinburgh• Communication between neurons is not typically a one-to-one event. –Sometimes a single neuron branches and its collaterals synapse on multiple

R Cheung MSc Bioelectronics: PGEE11106 1

Neurons

Pyramidal neurons in mouse cerebral cortex expressing green fluorescent protein.

The red staining indicates GABAergic interneurons.

MBL, Woods Hole

Page 2: Neurons - University of Edinburgh• Communication between neurons is not typically a one-to-one event. –Sometimes a single neuron branches and its collaterals synapse on multiple

R Cheung MSc Bioelectronics: PGEE11106 2

Neuron

• The functional and structural unit of the nervous system

• There are many different types of neurons, but most have

certain structural and functional characteristics in common

Dendrite

Nucleus

Axon

Hillock

Axon

Myelin sheath

Schwann cell

Node of

Ranvier

Axon terminal

Page 3: Neurons - University of Edinburgh• Communication between neurons is not typically a one-to-one event. –Sometimes a single neuron branches and its collaterals synapse on multiple

R Cheung MSc Bioelectronics: PGEE11106 3

Neurons are excitable cells specialized to conduct information from one part

of the body to another via electrical impulses conducted along their axons.

Function of Neurons

Medium: AXON

Message: ACTION POTENTIAL

Communication Model

Sender Receiver

Page 4: Neurons - University of Edinburgh• Communication between neurons is not typically a one-to-one event. –Sometimes a single neuron branches and its collaterals synapse on multiple

R Cheung MSc Bioelectronics: PGEE11106 4

Membrane Potentials: Signals

• Neurons use changes in membrane potential to

receive, integrate, and send information.

• Two types of signals are produced by a change

in membrane potential:

– Graded potentials (short-distance)

– Action potentials (long-distance)

Page 5: Neurons - University of Edinburgh• Communication between neurons is not typically a one-to-one event. –Sometimes a single neuron branches and its collaterals synapse on multiple

R Cheung MSc Bioelectronics: PGEE11106 5

-

+ + + + +

+ + + + +

- - - -

- - - -

-

-70 mV

Resting Axon Membrane Potential

The membrane potential is always given as the intracellular potential relative

to the extracellular potential - which is arbitrarily defined as zero.

Resting Neuron :

Membrane is polarized.

Inner, axoplasmic, side

is negatively charged.

All gated-sodium and

potassium channels are

closed.

Page 6: Neurons - University of Edinburgh• Communication between neurons is not typically a one-to-one event. –Sometimes a single neuron branches and its collaterals synapse on multiple

R Cheung MSc Bioelectronics: PGEE11106 6

Graded Potentials

• Short-lived, local changes in membrane potential

• Currents decrease in magnitude with distance

• Their magnitude varies directly with the strength of the stimulus

• The stronger the stimulus the more the voltage changes, the farther

the current goes, and more likely to initiate action potentials

- - - + - - - -

+ + +

+

+ + + +

+ + + - + + + +

- - -

- - - - -

Depolarization

stimulus

Spread of Depolarization

- - - - - -

+

+

+ +

+ + + +

+ +

+ + + + + +

- - - - -

-

- - -

-

Page 7: Neurons - University of Edinburgh• Communication between neurons is not typically a one-to-one event. –Sometimes a single neuron branches and its collaterals synapse on multiple

R Cheung MSc Bioelectronics: PGEE11106 7

Action Potentials (APs)

• Supra-threshold stimuli cause voltage-gated Na+

channels to open to produce depolarizing currents

• The AP is a brief reversal of membrane potential with a

total amplitude of ~100 mV (from -70mV to +30mV)

• APs do not decrease in strength with distance

All-or-Nothing - action potentials either

happen completely, or not at all

Page 8: Neurons - University of Edinburgh• Communication between neurons is not typically a one-to-one event. –Sometimes a single neuron branches and its collaterals synapse on multiple

R Cheung MSc Bioelectronics: PGEE11106 8

• Appropriate stimulus applied to

the resting axon triggers nerve

impulse/action potential

• Membrane becomes negative

externally

Signals Carried by Neurons

- - - - - - - -

+ + + + + + + +

+ + + + + + + +

- - - - - - - -

High [Na+]

High [K+]

Resting Membrane

- + - - - - - +

+ - + + + + + -

+ - + + + + + -

- + - - - - - +

[Na+]

Depolarization and generation

of the nerve impulse

• At the leading edge of the

impulse, ‘fast’ sodium gates open.

The membrane becomes more

permeable to Na+ ions and an

action potential occurs.

Page 9: Neurons - University of Edinburgh• Communication between neurons is not typically a one-to-one event. –Sometimes a single neuron branches and its collaterals synapse on multiple

R Cheung MSc Bioelectronics: PGEE11106 9

Signals Carried by Neurons

Propagation of the AP As the action potential passes,

slow potassium gates open,

allowing K+ ions to flow out. [Na+]

[K+]

+ - + + + + - -

- + - - - - + +

- + - - - - + +

+ - + + + + - -

[Na+]

Repolarization

Depolarization

The action potential continues

to move along the axon in the

direction of the nerve impulse.

Page 10: Neurons - University of Edinburgh• Communication between neurons is not typically a one-to-one event. –Sometimes a single neuron branches and its collaterals synapse on multiple

R Cheung MSc Bioelectronics: PGEE11106 10

The Dipole Field due to Current Flow in an Axon

at the Advancing Front of Depolarization.

Page 11: Neurons - University of Edinburgh• Communication between neurons is not typically a one-to-one event. –Sometimes a single neuron branches and its collaterals synapse on multiple

R Cheung MSc Bioelectronics: PGEE11106 11

Hyperpolarization

• The ‘slow’ K+ gates remain open longer than needed to restore

the resting state.

• This excessive efflux causes hyperpolarization of the

membrane.

• The axon is insensitive to stimulus and depolarization during

this time.

Page 12: Neurons - University of Edinburgh• Communication between neurons is not typically a one-to-one event. –Sometimes a single neuron branches and its collaterals synapse on multiple

R Cheung MSc Bioelectronics: PGEE11106 12

Role of the Sodium-Potassium Pump

• Repolarization restores the resting electrical

conditions of the axon, but does not restore the

resting ionic conditions.

• Ionic redistribution is accomplished by the sodium-

potassium pump following repolarization.

Page 13: Neurons - University of Edinburgh• Communication between neurons is not typically a one-to-one event. –Sometimes a single neuron branches and its collaterals synapse on multiple

R Cheung MSc Bioelectronics: PGEE11106 13

Refractory Periods • Absolute Refractory Period: Time between opening and

closing of the Na+ activation gates. The axon cannot respond

to another stimulus.

• Relative Refractory Period: Follows the absolute refractory

period. Na+ gates are closed, K+ gates are open and

repolarization is occurring. Only a strong stimulus can

generate an AP.

stimulus

0

+30 mV

-70 mV

-55 mV

Absolute RP Relative RP

Page 14: Neurons - University of Edinburgh• Communication between neurons is not typically a one-to-one event. –Sometimes a single neuron branches and its collaterals synapse on multiple

R Cheung MSc Bioelectronics: PGEE11106 14

Axon Conduction Velocities

• Conduction velocities vary widely among

neurons, determined mainly by:

– Axon Diameter - the larger the diameter, the faster

the impulse (less resistance)

– Presence of a Myelin Sheath – myelination

increases impulse speed (Continuous vs. Saltatory

Conduction)

Page 15: Neurons - University of Edinburgh• Communication between neurons is not typically a one-to-one event. –Sometimes a single neuron branches and its collaterals synapse on multiple

R Cheung MSc Bioelectronics: PGEE11106 15

Saltatory Conduction

• Gaps in the myelin sheath between adjacent Schwann cells are called nodes of Ranvier.

• Voltage-gated Na+ channels are concentrated at these nodes.

• Action potentials are triggered only at the nodes and jump from one node to the next.

• Much faster than conduction along unmyelinated axons.

Axon Myelin sheath

Node of

Ranvier [Na+]

[Na+]

Page 16: Neurons - University of Edinburgh• Communication between neurons is not typically a one-to-one event. –Sometimes a single neuron branches and its collaterals synapse on multiple

R Cheung MSc Bioelectronics: PGEE11106 16

• As the impulse reaches the axon terminals the signal is relayed

to target cells at specialized junctions known as synapses.

• Arrival of impulse at synapse opens Ca2+ channels.

• Neurotransmitter is released into the synaptic cleft via

exocytosis.

• Neurotransmitter crosses the synaptic cleft and binds to

receptors on the postsynaptic neuron.

• Postsynaptic membrane permeability changes due to opening

of ion channels, causing an excitatory or inhibitory effect.

Information Transfer at Synapse

Page 17: Neurons - University of Edinburgh• Communication between neurons is not typically a one-to-one event. –Sometimes a single neuron branches and its collaterals synapse on multiple

R Cheung MSc Bioelectronics: PGEE11106 17

Synaptic Transmission

• An AP reaches the axon terminal of

the presynaptic cell and causes V-

gated Ca2+ channels to open.

• Ca2+ rushes in, binds to regulatory

proteins & initiates neurotransmittier

(NT) exocytosis.

• NTs diffuse across the synaptic cleft

and then bind to receptors on the

postsynaptic membrane and initiate

some sort of response on the

postsynaptic cell.

Page 18: Neurons - University of Edinburgh• Communication between neurons is not typically a one-to-one event. –Sometimes a single neuron branches and its collaterals synapse on multiple

R Cheung MSc Bioelectronics: PGEE11106 18

Neurotransmitter Removal

• NTs are removed from the

synaptic cleft via:

– Enzymatic degradation

– Diffusion

– Reuptake

Page 19: Neurons - University of Edinburgh• Communication between neurons is not typically a one-to-one event. –Sometimes a single neuron branches and its collaterals synapse on multiple

R Cheung MSc Bioelectronics: PGEE11106 19

• Different neurons can contain different NTs.

• Different postsynaptic cells may contain different receptors.

– Thus, the effects of an NT can vary.

• Some NTs cause cation channels to open, which results in a

graded depolarization.

• Some NTs cause anion channels to open, which results in a

graded hyperpolarization.

Effects of the Neurotransmitter

Page 20: Neurons - University of Edinburgh• Communication between neurons is not typically a one-to-one event. –Sometimes a single neuron branches and its collaterals synapse on multiple

R Cheung MSc Bioelectronics: PGEE11106 20

• Typically, a single synaptic interaction will not create a graded

depolarization strong enough to migrate to the axon hillock and

induce the firing of an AP

– However, a graded depolarization will bring the membrane

potential closer to threshold. This is referred to as an

excitatory postsynaptic potential.

– Graded hyperpolarizations bring the membrane potential

farther away from threshold and thus are referred to as

inhibitory postsynaptic potentials.

• Whether a transmitter is excitatory or inhibitory depends on

its receptor.

Excitatory and Inhibitory Neurotransmitters

Page 21: Neurons - University of Edinburgh• Communication between neurons is not typically a one-to-one event. –Sometimes a single neuron branches and its collaterals synapse on multiple

R Cheung MSc Bioelectronics: PGEE11106 21

• Acetylcholine is excitatory because its receptor is

a ligand-gated Na+ channel.

• GABA is inhibitory because its receptor is a

ligand-gated Cl- channel.

• Other transmitters (e.g. vasopressin, dopamine)

have G-protein-linked receptors.

– Effects depend on the signal transduction pathway and

cell type.

Excitatory and Inhibitory Neurotransmitters

Page 22: Neurons - University of Edinburgh• Communication between neurons is not typically a one-to-one event. –Sometimes a single neuron branches and its collaterals synapse on multiple

R Cheung MSc Bioelectronics: PGEE11106 22

Temporal Summation

• One Excitory Postsynaptic Potential (EPSP) is usually not strong enough to cause an Action Potential. However, EPSPs may be summed:

• Temporal summation - the same presynaptic neuron stimulates the postsynaptic neuron multiple times in a brief period. The depolarization resulting from the combination of all the EPSPs may cause an AP.

• Spatial summation - multiple neurons all stimulate a postsynaptic neuron resulting in a combination of EPSPs which may yield an AP.

0

+30 mV

-70 mV

-55 mV

stimulii

EPSPs

Page 23: Neurons - University of Edinburgh• Communication between neurons is not typically a one-to-one event. –Sometimes a single neuron branches and its collaterals synapse on multiple

R Cheung MSc Bioelectronics: PGEE11106 23

• Communication between neurons is not typically a one-to-one event.

– Sometimes a single neuron branches and its collaterals synapse on multiple target neurons. This is known as divergence.

– A single postsynaptic neuron may have synapses with as many as 10,000 presynaptic neurons. This is convergence.

Synaptic Organization

Divergence

Convergence

Page 24: Neurons - University of Edinburgh• Communication between neurons is not typically a one-to-one event. –Sometimes a single neuron branches and its collaterals synapse on multiple

R Cheung MSc Bioelectronics: PGEE11106 24

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