1. 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

2. 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)

3. 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

4. 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

5. 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 non-neuronal 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.

6. 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.

8. Membranous Organelles in the Neurons
Rough endoplasmic reticulum (rough ER)
Smooth endoplasmic reticulum (smooth ER)
Golgi apparatus
Nuclear envelop
Mitochondria (energy) and peroxisomes (detoxification)

10. Selective Distribution of Membranous Organelles in Neurons
A sharp functional boundary at the axon hillock, certain organelles are absent in axon
protein biosynthetic machinery (ribosomes, rough ER, Golgi complex).
lysosomes
Axons are rich in
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.

11. 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

12. 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.

13. Fig.4-3. Golgi complex appears
as a network of filaments that
extend into dendrites (arrow)
but not into the axon
dendrite
axon

14. 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 pre- and post-synaptic morphological specializations

15. Microtubules subunits: a- and b-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)
mostly to stabilize or enhance microtubule assembly
axon: tau (causing microtubules to form tight bundles in axon) and MAP3
dendrite: MAP2 13

16. Expression of the Genes for Tau and MAP2C in a Nonneuronal Cell Line
Sf9 is an insect cell line that is non-neuronal.
Sf9 cells expressing
tau protein
Sf9 cells expressing
MAP2C protein
normal Sf9 cells

17. Neurofilaments
cytokeratin family including glial fibrillary acidic protein (GFAP)
10 nm in diameter
stable polymers
neurofibrillary tangle in Alzheimer’s disease patients
1 neurofilament  32 monomer
8 protofilaments in each neurofilament
4 monomers in each protofilament

18. Microfilaments subunits: b- and g-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.

19. In dendrites, microtubules with opposite polarities are mixed.
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
a-tubulin
b-tubulin (G)
GTP
25-28 nm
dynamic but more stable in mature axons and dendrites
neurofilament
cytokeratins
GFAP etc (F)
none
10 nm
stable and polymerized
microfilament
b-actin
g-actin (G)
ATP
3-5 nm
dynamic, ～ ½ of the actin in neurons can be unpolymerized

21. 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 ( mm) 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.

23. 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

24. 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

25. 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.

26. Extensive dendritic structure of a cat spinal motor neuron

27. 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.

28. IS: initial segment
AH: axon hillock

29. 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)

30. 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

31. The information flow from sensory to motor neurons is…
Divergent- each sensory neuron contact 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

32. 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.

33. 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.

35. 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 mm
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 mm from CA1
neuron’s cell body. B. A single
CA3 axon forms synapses on
dendrites 259 mm from the cell
body. C. A single CA3 axon form
synapses on two dendrites 263
mm from the cell body.
CA3
CA3
CA3
CA1
CA3

36. 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.

37. 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.

38. 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.

40. 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.

41. 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 over-production of this Schwann cell protein.

42. An Overall View Four distinctive compartments in nerve cells
Cell body – protein synthesis
Axon – projection over long distances to target cells
Dendrites – receiving signal from other neurons
Nerve terminals – release of neurotransmitters at synapses with targets