Download Chapter 4: The Cytology of Neurons

Chapter 4: The Cytology of Neurons
Principles of Neural Science by Eric R.
Kandel
Fundamental Neuroscience by Duane E.
Haines
The World of the Cell by Wayne M.
Becker
楊定一 (Ding-I Yang)
圖資大樓851室 分機7386
An Overall View
The Structural and Functional Blueprint of
Neurons is Similar to Epithelial Cells
Membranous Organelles Are Selectively
Distributed Throughout the Neuron
The Cytoskeleton Determines the Shape of the
Neuron
The Neurons That Mediate the Stretch Reflex
Differ in Morphology and Transmitter
Substance (sensory neurons and motor
neurons)
An Overall View (continued)
Pyramidal Neurons in the Cerebral
Cortex Have More Extensive Dendritic
Trees Than Spinal Motor Neurons
Glial Cells Produce the Insulating Myelin
Sheath Around Signal-Conducting Axons
Common Features of Neurons That
Differ from Other Tissues
Neurons are highly polarized
The cell function of neurons are
compartmentalized, contributing to the
processing of electrical signals
-cell body (soma): RNA/proteins synthesis
-dendrites: thin processes to receive
synaptic input from other neurons
-axons: another thin process to propagate electric
impulse
-terminals: for synaptic output
Common Features of Neurons That
Differ from Other Tissues (continued)
Neurons are excitable due to specialized
protein structures, including ion channels
and pumps, in the membrane.
Although polarity (epithelial and other nonneuronal secretory cells) and excitability
(muscle) are not unique to neurons, they are
developed to a higher degree allowing
signal to be conducted over long distance.
Neurons Develop from Epithelial Cells
Axon arises from “apical surface”; dendrites arise
from “basolateral surface”.
Plasmalemma: external cell membrane of a neuron
cytoplasm = cytosol (aqueous phase and cytoskeletal
matrix) + membranous organelles (vacuolar
apparatus, mitochondria, and peroxisomes)
Most of the cytosolic proteins are common to all the
neurons. However, certain enzymes involved in the
synthesis or degradation of neurotransmitters are
specifically synthesized in selected neurons. For
example, acetylcholinesterase is only found in
cholinergic neurons.
Membranous Organelles in the Neurons
z Rough
endoplasmic reticulum (rough
ER)
z Smooth endoplasmic reticulum
(smooth ER)
z Golgi apparatus
z Nuclear envelop
z Mitochondria (energy) and
peroxisomes (detoxification)
Selective Distribution of Membranous
Organelles in Neurons
A sharp functional boundary at the axon hillock,
certain organelles are absent in axon
z
z
protein biosynthetic machinery (ribosomes, rough
ER, Golgi complex).
lysosomes
Axons are rich in
z
z
z
synaptic vesicles
endocytic intermediates involved in synaptic vesicle
traffic
synaptic vesicle precursor membranes
Mitochondria and smooth ER (Ca2+ regulation) are
present in all neuronal compartment including
axon.
Fig.4-2. Endoplasmic reticulum in
a pyramidal cell showing a basal
pole. A single dendrite emerges
from the cell body.
Golgi
Dendrite
Golgi
ER
Nucleus
Selective Distribution of Membranous
Organelles in Neurons
The cytoplasm of the cell body extends into
the dendritic tree without any functional
boundary. However, concentrations of some
organelles such as rough ER, Golgi, and
lysosomes progressively diminish into
dendrites.
Fig.4-3. Golgi complex appears
as a network of filaments that
extend into dendrites (arrow)
but not into the axon
dendrite
axon
The Cytoskeletal Structures of Neurons
The Cytoskeleton Determines the Shape of the
Neuron
– Microtubules: developing and maintaining the
neuron’s processes
– Neurofilaments: bones of the cytoskeleton; the most
abundant fibrillar components of the axon; on
average 3-10 times more abundant than microtubules
in an axon
– Microfilaments: short polymers concentrated at the
cell’s periphery lying underneath plasmalemma. This
matrix plays important roles in the formation of preand post-synaptic morphological specializations
Microtubules
subunits: α- and β-tubulin
25-28 nm in diameter
polar, dynamic structure
tubulin is a GTPase; microtubules
grow by addition of GTP-bound
tubulin dimers at plus end.
microtubule-associated protein (MAP)
z mostly to stabilize or enhance
microtubule assembly
z axon: tau (causing microtubules
to form tight bundles in axon)
and MAP3
z dendrite: MAP2
13
Expression of the Genes for Tau and MAP2C
in a Nonneuronal Cell Line
Sf9 is an insect cell line that is non-neuronal.
normal Sf9 cells
Sf9 cells expressing
tau protein
Sf9 cells expressing
MAP2C protein
Neurofilaments
cytokeratin family including
glial fibrillary acidic protein
(GFAP)
10 nm in diameter
stable polymers
neurofibrillary tangle in
Alzheimer’s disease patients
1 neurofilament Ù 32
monomer
z
z
8 protofilaments in each
neurofilament
4 monomers in each
protofilament
Microfilaments
subunits: β- and γ-actin monomer
3-5 nm in diameter
polar, dynamic structure
ATP
With actin-binding proteins, actin
filaments form a dense network lying
underneath the plasmalemma. This
matrix plays a key role in the
formation of pre- and postsynaptic
morphologic specializations.
Microtubules and actin filament act as tracks for
intracellular protein and organelle movement
In axon, all the microtubules are arranged with the
plus end pointing away from the cell body, minus end
facing the cell body.
In dendrites, microtubules with opposite polarities are
mixed.
microtubule
α-tubulin
β-tubulin (G)
neurofilament
cytokeratins
GFAP etc (F)
microfilament
β-actin
γ-actin (G)
GTP
none
ATP
25-28 nm
10 nm
3-5 nm
dynamic but
more stable in
mature axons
and dendrites
stable and
polymerized
dynamic, ∼ ½
of the actin in
neurons can be
unpolymerized
The neurons that mediate the stretch
reflex differ in morphology and
transmitter substance
Sensory neurons convey information about the state of
muscle contraction. The cell bodies are round with large
diameter (60-120 µm) located in dorsal root ganglia. The
pseudo-unipolar neuron bifurcates into two branches from
cell body. The peripheral branch projects to muscle. The
central branch project to spinal cord, where it forms
synapses on dendrites of motor neurons.
Motor neurons convey central motor commands to the
muscle fiber. Unlike sensory neurons which have no
dendrites, motor neurons have several dentritic trees.
When excited, the sensory
neuron releases excitatory
amino acid neurotransmitter
L-glutamate that depolarizes
the motor neurons.
Orange: sensory axons enter
the spinal cord and
Green: dendrites of motor
neurons
The sensory neuron conducts information from the
periphery to the central nervous system
Fig. 4-8A: The axon of the
sensory neuron bifurcates
into a central and a
peripheral branch. Sc,
Schwann cells; Nuc,
nucleolus; N, nucleus.
Fig. 4-8B: Motor neuron.
Left, many dendrites
typically branch from the
cell bodies of spinal motor
neurons, as shown by five
spinal motor neurons in
the ventral horn of a kitten.
Right, “synaptic bouton”,
a knob-like enlargement
on the cell membrane
where nerve endings from
presynaptic neurons
attach.
den
den
Dendrites of Motor Neurons
Dorsal root ganglion sensory neurons have no
dendrites, but motor neurons have several dendritic
trees that arise directly from the cell body.
Short specialized dendritic extensions, or spines,
serve to increase the area of the neuron available for
synaptic inputs.
Dendrites are functional extensions of the cell body
with protein synthesis. The mRNA is transported
along dendrites and appears to concentrated at the
base of dendritic spines.
Extensive dendritic structure of a cat spinal motor neuron
The Morphological Characteristics of
Motor Neurons
Axon hillock: where each motor neuron gives rise to
its only one axon.
Synaptic boutons: the knob-like terminals of the
axons of presynaptic neurons.
Trigger zone: axon hillock and initial segment
(unmyelinated) of the axon where incoming signals
from other neurons are integrated and the action
potential is generated.
Recurrent collateral branches: the branches of the
axon project back to the motor neuron and modify its
own activity.
IS: initial segment
AH: axon hillock
Motor neuron can receive signal
inputs from…
Excitatory input from primary sensory neurons
Recurrent collateral branches of its own
Recurrent excitatory input from other motor
neuron
Both excitatory and inhibitory input from
interneurons driven by descending fibers from
brain that control and coordinate movement
Inhibitory input from Renshaw cells (an
interneuron in spinal cord using L-glycine as
neurotransmitters)
The difference between
sensory neurons and motor neurons
no dendrites
L-glutamate
pseudo-unipolar
has few if any boutons
on its cell body; primary
input from sensory
receptors at the terminal
of peripheral branch
extensive dendritic
structures
acetylcholine
multipolar
receive inputs throughout
its dendrites and cell body,
with inhibitory synapses on
the cell body close to trigger
zone and excitatory ones
located farther out along the
dendrites
The information flow from
sensory to motor neurons is…
Divergent- each sensory neuron contact
500-1000 motor neurons with 2-6
synapses on each motor neuron
Convergent- each motor neuron receives
input from many sensory neurons; more
than 100 sensory neurons are required to
reach firing threshold of action potential
Pyramidal neurons in cerebral cortex have
more extensive dendritic trees than spinal
motor neurons
Motor neurons are the major excitatory projection
neurons in spinal cord. Pyramidal cells are the
excitatory projection neurons in the cerebral cortex
using L-glutamate as neurotransmitter.
Pyramidal cells have not one but two dendritic trees
emerging from opposite sides of the cell body: basal
dendrites (the same side that gives rise to axon) and
apical dendrites
The Schaffer collaterals (CA3 pyramidal cell axons)
form en passant synapses with CA1 dendrites.
Pyramidal neurons in cerebral cortex have
more extensive dendritic trees than spinal
motor neurons
Hippocampus (for processing memory
formation) is divided into two major regions,
CA1 and CA3. The cell bodies of pyramidal
cells are situated in a single continuous layer,
the stratum pyramidale.
The axons of pyramidal neurons run in the
stratum radiatum.
CA1
Fig. 4-15 Pyramidal cells in the
CA3 region of the hippocampus
form synapses on the dendrites of
CA1 cells in the stratum radiatum
Left: Golgi-stained CA1
pyramidal cells with dendrites
extending downward 350 µm
into stratum radiatum.
Right: Three micrographs show
synapses formed on this CA1
cell by CA3 cells. A. Axons of
two CA3 neurons form synapses
on a dendrite 50 µm from CA1
neuron’s cell body. B. A single
CA3 axon forms synapses on
dendrites 259 µm from the cell
body. C. A single CA3 axon form
synapses on two dendrites 263
µm from the cell body.
CA1
CA3
CA3
CA3
CA1
CA3
The spines on the CA1
pyramidal cells have
only excitatory synapse.
Four types of spines
in the dendrites of
pyramidal cells in CA1
region: thin, stubby,
mushroom, branched.
The neck of the spine
restricts diffusion
between the head and
the rest of dendrites.
Each spine may function
as a separate biochemical
region.
Glial Cells Produce the Insulating Myelin
Sheath Around Signal-Conducting Axons
Myelin has a biochemical composition of 70%
lipid and 30% protein that is similar to plasma
membrane.
Peripheral nerve is myelinated by Schwann
cells. Each internodal (node of Ranvier)
segment represents a single Schwann cells. The
expression of myelin genes is regulated by the
contact between the axon and the myelinating
Schwann cells.
Glial Cells Produce the Insulating Myelin
Sheath Around Signal-Conducting Axons
In CNS, the central branch of dorsal root ganglion
cell axons and motor neurons are myelinated by
oligodendrocyte. Unlike Schwann cells, each
oligodendrocyte ensheathes several axon processes.
Expression of myelin genes by oligodendrocyte
depends on the presence of astrocyte, the other
major type of glial cells in CNS.
Shiverer mutant mice: an animal model for
demyelination diseases
The shiverer mice have tremors and
frequent convulsions, often died at
young ages.
Five out of six exones of myelin basic
protein (MBP) are deleted in shiverer
mice, with only 10% of MBP as
compared to normal mice. As a
result, myelination is incomplete in
these mutant mice.
Transgenic shiverer mice expressing
normal MBP gene has improved
myelination. Despite occasional
tremors, these mice do not have
convulsions and live a normal life
span.
Charcot-Marie-Tooth Disease
This disease is
characterized by
progressive muscle
weakness, greatly
decreased conduction
in peripheral nerves,
as well as cycles of
demyelination and
remyelination.
Duplication of
peripheral myelin
protein (PMP22)
gene on chromosome
17 causing overproduction of this
Schwann cell protein.
An Overall View
Four distinctive compartments in nerve cells
Cell body – protein synthesis
z Axon – projection over long distances to target
cells
z Dendrites – receiving signal from other neurons
z Nerve terminals – release of neurotransmitters at
synapses with targets
z