Neurons

Neurobiology
Cells of the nervous system
Anthony Heape
2010
1
The nervous system
• Central nervous system (CNS)
• Peripheral nervous system (PNS)
2
Enteric nervous system
(digestive tract, gall
bladder and pancreas)
Functional sub-divisions
of the nervous system
Afferent = carry towards
Efferent = carry away from
3
Cells of the nervous system
Neurons
Neuroglia
 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
 Astrocytes
 Structural classification
 Multipolar
 Bipolar
 (pseudo-) unipolar
 Radial glia (embryonic)
 Ependymal Cells
 Microglia
 Oligodendrocytes
 Schwann cells
 Satellite cells
Polarity is defined as the number of a neuron’s own
processes (extensions) that are directly associated with
the cell body (soma)
4
Cells of the nervous system
Neurons
The excitable cells of the nervous system that transmit
electrochemical signals from one cell to another
5
Neurons
Morphology
6
Neuronal
morphology
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.
Examples of Multipolar cells
 Pyramidal cells in the cerebral cortex
 Purkinje cells, stellate cells, granular cells and
basket cells in the cerebellum
7
Cells of the
Cerebellum
8
Cerebellum
100X
Granule Cells
Golgi stain
400X
Granular
layer
Molecular
layer
H & E stain
400X
silver stain
Purkinje cells
Molecular
layer
Granular
9
layer
Purkinje cells fluorescently
labelled with GFP
Santiago Ramón y Cajal (1905)
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.
10
Cerebellum
Molecular layer
Cerebral cortex
Cerebral
cortex
Molecular
layer
Pyramidal Cells
Stellate Cells
11
Spinal cord anterior horn
motor neurons
(multipolar)
Dorsal root ganglion
sensory neurons
(pseudounipolar)
SILVER STAIN
(BIELSCHOWSKY)
400X
800X
12
Retina
(bipolar neurons)
Bipolar
neurons
13
Neurons
Structure
A 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”
14
Typical
neurons
Myelin
sheath
15
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”)
16
Special features of the neuronal soma
Nissl
bodies
(pink)
Lipofuscin
granules
(blue/yellow)
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 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.
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.
17
The
neuronal
processes
Axon (only 1)
Dendrites
18
Dendrites
axon (sensory input)
dendrites
axo-dendritic synapses
axon
collateral axon
dendrites
axo-somatic synapse
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.
axon (motor output)
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.
19
Dendrites and Dendritic spines
Each 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).
”Low” power
LM
EM
”High” power
LM 3D
reconstruction
Confocal
microscopy
with GFP
The spine
apparatus
Specialization
of the smooth
endoplasmic
reticulum
responsible for
the release of
calcium in
response to
receptor
activity
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.
20
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?
21
Special features of axons
the axon hillock
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.
22
Special features of axons
The axon starts from the axon hillock.
The axon can be short, or as long as 1 metre, or more.
Branches (axon collaterals) along
length are infrequent.
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 voltagesensitive sodium ion (Na+) channels along the whole length of
their plasma membrane (axolemma).
Multiple terminal branches
(telodendria) at end of axon end in
knobs, called axon terminals (also
“end bulbs”, or “boutons”).
telodendria
1 mm (1000 nsec)
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
23
action potentials from the hillock to the axon terminals.
Neuronal signalling



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)
Voltage-sensitive (-gated) ion
channels allow depolarization
Excitatory signal

Signals occur as changes in membrane potential

Stimulation:
depolarisation

Inhibition:
hyperpolarisation
Inhibitory signal
24
Neuronal signalling potentials
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.
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.
25
Propagation of the
nervous impulse
1
2
3
4
5
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. 26
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, ...).
27
Neuromuscular Junction
100x
400x
Axon
telodendria
NMJ
NMJ
skeletal
muscle fiber
Axon
terminal
Synapse
28
Excitatory and inhibitory
signaling across synapses:
The neuro-muscular junction
29
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.
Examples of neurotransmitters
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.
30
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
31