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Neurobiology

Anthony Heape

2010

Cells of the nervous system

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The nervous system

• Central nervous system (CNS)

• Peripheral nervous system (PNS)

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En

teri

c n

erv

ou

s s

ys

tem

(dig

es

tive

tra

ct,

ga

ll

bla

dd

er

an

d p

an

cre

as

)

Afferent = carry towards

Efferent = carry away from

Functional sub-divisions

of the nervous system

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Cells of the nervous system

Polarity is defined as the number of a neuron’s own

processes (extensions) that are directly associated with

the cell body (soma)

Neurons

Functional classification

Sensory or afferent: Action

potentials toward CNS

Motor or efferent: Action

potentials away from CNS

Interneurons or association

neurons: Within CNS from one

neuron to another

Structural classification Multipolar Bipolar (pseudo-) unipolar

Neuroglia

Astrocytes

Ependymal Cells

Microglia

Oligodendrocytes

Schwann cells

Satellite cells

Radial glia (embryonic)

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Cells of the nervous system

NeuronsThe excitable cells of the nervous system that transmit

electrochemical signals from one cell to another

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Neurons

Morphology

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Neuronal

morphology

Examples of Multipolar cells

Pyramidal cells in the cerebral cortex

Purkinje cells, stellate cells, granular cells and

basket cells in the cerebellum

Multipolar: most neurons (e.g. motor

neurons, interneurons/association neurons)

Pseudounipolar: these are always

sensory neurons, but not all sensory

neurons are pseudounipolar.

Bipolar: most rare, associated with some

sense organs; retina, olfactory mucosa

and inner ear.

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Cells of the

Cerebellum

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100X

silv

er s

tain

400X

H & E stain

Purkinje cells

Cerebellum

400X

Golgi stain

Granule Cells

Molecular

layer

Granular

layer

Molecular

layer

Granular

layer

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Purkinje cells fluorescently

labelled with GFP

In images acquired by normal light

microscopy, it is rare to see more

than a few (if any) processes of a

given cell, but, even without GFP,

Ramón y Cajal didn’t miss much

detail in his drawings.

Santiago Ramón y Cajal (1905)

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Cerebral cortex

Pyramidal Cells Stellate Cells

Cerebellum

Molecular layer

Cerebral

cortexMolecular

layer

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Spinal cord anterior horn

motor neurons

(multipolar)

SILVER STAIN

(BIELSCHOWSKY)

400X

Dorsal root ganglion

sensory neurons

(pseudounipolar)

800X

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Retina

(bipolar neurons)

Bipolar

neurons

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Neurons

StructureA typical neuron has:

Cell body (or soma) with nucleus &

organelles

Dendrites to receive information (from

another neuron).

Axon to carry information to another cell

(another neuron, muscle, gland), with which

it communicates via a synapse.

In histological sections, it is often difficult to

distinguish between dendrites and axons.

They are thus often referred to as ”processes”

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Typical

neurons

Myelin

sheath

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The

neuronal

soma

The soma (or perikaryon) contains:

• a single nucleus, with a prominent nucleolus (site of ribosome synthesis)

• Most normal cellular organelles are also present:

Mitochondria

Golgi apparatus

Endoplasmic reticulum, etc.

Karyon = nucleus (literally, ”nut”)

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Special features of the neuronal soma

Nissl bodies can be demonstrated by a method of selective staining developed by Nissl, to label extranuclear RNA granules. This staining method is useful to localize the perikaryon, as it can be seen in the soma and dendrites of neurons, though not in the axon, nor in the axon hillock.

The soma contains a very

active and highly developed

rough endoplasmic

reticulum (responsible for the

synthesis of proteins) that has

a granular appearance.

These granules are referred

to as Nissl bodies.

Nissl

bodies

(pink)

Lipofuscin

granules

(blue/yellow)

Neurofibrils – Abundant

network of protein filament

bundles, which help maintain

the shape, structure, and

integrity of the cell.

Lipofuscin granules

accumulate with age around

the nucleus and represent

lipid-containing degradation

products, often referred to as

“wear-and-tear” pigments.

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The

neuronal

processes

Dendrites

Axon (only 1)

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Dendrites

collateral axon

axon (motor output)

dendrites

axo-dendritic synapses

axo-somatic synapse

axon

axon (sensory input)

dendrites

A dendrite is a neuronal

process (usually short, with

multiple branches) emerging

from the soma, and through

which the soma of a neuron

receives signals from other

neurons, and transmits it to

the rest of the neuron via

(short-range) graded

potentials (≠ action potentials).

Note: dendrites do not have

a myelin sheath and contain

no neurofibrils.

Myelin = insulating multilamellar membrane sheath around axons of

CNS & PNS neurons. It allows a faster transmission of

action potentials along the nerve fibre.

Synapse = specialized junction between a neuronal axon and another

cell, across which a (bio)chemical signal is transmitted.

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3D reconstructions of a

dendrite (above) and

dendritic spines (above and

left). Excitatory (red) and/or

inhibitory (blue) synapse

regions are located on the

head of the spine.

The spine apparatus

(brown) is located in the

head and neck of the spine.

Dendrites and Dendritic spinesEach dendrite presents many small membranous protrusions, called dendritic spines, along its whole length. There can be as many as 103 – 105 (e.g. in Purkinje cells) dendritic spines/neuron.

Each dendritic spine typically receives (inhibitory or excitatory) input from a single axon, but sometimes two (one inhibitory and one excitatory).

The spine

apparatus

Specialization

of the smooth

endoplasmic

reticulum

responsible for

the release of

calcium in

response to

receptor

activity

”High” power

LM 3D

reconstruction

”Low” power

LMConfocal

microscopy

with GFP

EM

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Axons

Axons

An axon is a neuronal

process (often long, with few

collateral branches) emerging

from the soma, and through

which the neuron transmits

signals towards another cell

(neuron, muscle, gland, ...), by

means of action potentials.

A neuron always has one

axon that, typically, transmits

signals away from the

neuronal soma.

The ”peripheral axons” of

(pseudo-unipolar) sensory

neurons are exceptions: are

they in fact dendrites?

?

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Special features of axons

the axon hillock

The axon hillock has no Nissl bodies.

Multiple signals generated at the

dendritic spines, and transmitted by the

soma, all converge at the axon hillock.

The axon hillock has a very high

concentration of voltage-activated Na+

channels.

The axon hillock is generally considered

to be the spike initiation zone for action

potentials.

Axon hillock

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Special features of axons

The axon can be short, or as long as 1 metre, or more.

Neurofilaments, actin microfilaments, and microtubules

provide structural support and aid in the transport of

substances to and from the soma (axonal transport).

Axons contain numerous mitochondria, as well as voltage-

sensitive sodium ion (Na+) channels along the whole length of

their plasma membrane (axolemma).

The axon starts from the axon hillock.

Branches (axon collaterals) along

length are infrequent.

Multiple terminal branches

(telodendria) at end of axon end in

knobs, called axon terminals (also

“end bulbs”, or “boutons”).

The Na+ channels are either distributed uniformly over the

whole axolemma, or clustered in “bands” spaced at ( ) regular

intervals along the axon, at the “nodes of Ranvier”.

These ion channels are responsible for the propagation of the

action potentials from the hillock to the axon terminals.

telodendria

1 mm (1000 nsec)

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Plasma membranes of neurons conduct

electrical signals

Resting neuron – membrane is polarized

Inner, cytoplasmic side (axoplasm) is negatively

charged (~ 70 mV, normal range of -60 to -90 mV)

Signals occur as changes in membrane potential

Stimulation: depolarisation

Inhibition: hyperpolarisation

Inhibitory signal

Excitatory signal

Neuronal signalling

Voltage-sensitive (-gated) ion

channels allow depolarization

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Local (graded) potentials

Local potentials result from

Ligands binding to receptors

Changes in charge across membrane

Mechanical stimulation

Temperature changes

Spontaneous change in membrane

permeability

Local potentials are “graded” membrane

depolarisations

Magnitude varies from small to “large”

depending on stimulus strength or frequency

Local potentials can summate (= add onto) each

other, eventually creating an action potential.

Neuronal signalling potentials

Action potentials A series of self-propagating permeability

changes occurring when a local potential causes depolarization of membrane that exceeds the threshhold for opening the axonal voltage-gated Na+ channels.

Phases of the action potential include

Depolarization: the axoplasm becomes more positive due to “massive” influx of Na+ ions.

Repolarization: the axoplasm becomes more negative due exit of K+ ions from the axoplasm.

Action potentials follow the all-or-nothing principle.

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1. Resting potential (-70 mV): High Na+ and low K+ outside, low Na+, high K+ inside.

2. Arrival of Na+ (positive charge) depolarisation wave from upstream in axoplasm

• Opens voltage-gated Na+ channels and some K+ channels.

• Allows massive influx of Na+ ions from outside, and exit of K+ ions from inside,

• Resulting in depolarisation (activates channels further downstream).

3. Depolarisation causes voltage-gated Na+ channels to close, and remaining K+ channels to open.

• K+ ions continue to leave

• Resulting in repolarisation.

4. And hyperpolarisation (over-shoot)

5. K+ channels close. K+ is outside and Na+ is inside

• The membrane is now refractory (non-responsive) to further stimulation.

Active (ATP-dependant) Na+ (outward) and K+ (inward) pumps return the membrane to an excitable state.

1 2 3 4 5

Propagation of the

nervous impulse

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Special features of axons

the axon terminals and synapses

The axon terminals transform the action potentials

arriving along the axon into a chemical signal, which is

transmitted across a synapse to another cell via

substances called neurotransmitters.

Neurotransmitters are synthesized in the axon terminal,

where they are accumulated (to high concentrations) and

stored in synaptic vesicles.

When the action potential arrives at the axon terminal,

the synaptic vesicles fuse with the presynaptic

membrane, releasing the neurotransmitter into the

synaptic cleft.

Receptors on ion channels of the

postsynaptic (plasma) membrane of the

target cell bind the neurotransmitter and

generate a cell-specific response by the

target cell (e.g. generation of a graded

potential in neurons, muscle fibre

contraction, ...).

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Neuromuscular Junction

NMJNMJ

skeletal

muscle fiber

100x 400x

Axon

terminal

Synapse

Axon

telodendria

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Excitatory and inhibitory

signaling across synapses:

The neuro-muscular junction

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Excitatory and inhibitory signaling

across synapses

Excitatory neurotransmitters open channels in the postsynaptic

membrane and leads to an increase in the concentration of Na+

ions within the postsynaptic cell, leading to a depolarisation of

the postsynaptic cell, and an active response.

Inhibitory neurotransmitters encourage the hyperpolarization of

the postsynaptic cell, making it less likely to respond.

Neurotransmitters, and their effects, may be specific to

particular target organs and have multiple roles around the

body.

E.g. Acetylcholine can be either excitatory to skeletal muscle

cells, or inhibitory to both smooth muscle and cardiac muscle.

Acetylcholine voluntary movement of the skeletal muscles and movement of the viscera

Glutamate the most abundant excitatory neurotransmitter in the central nervous system.

GABA the most abundant inhibitory neurotransmitter in the central nervous system.

Examples of neurotransmitters

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Cells of the nervous system

Neuroglia (or glial cells)The non-excitable cells of the nervous system that provide support to neuronal survival and function