Chapter 4: The Cytology of Neurons

Principles of Neural Science by Eric R. KandelFundamental Neuroscience by Duane E. HainesThe 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 NeuronThe 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)

Pyramidal Neurons in the Cerebral Cortex Have More Extensive Dendritic Trees Than Spinal Motor NeuronsGlial Cells Produce the Insulating Myelin Sheath Around Signal-Conducting Axons

An Overall View (continued)

Common Features of Neurons That Differ from Other Tissues

Neurons are highly polarizedThe 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

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.

Common Features of Neurons That Differ from Other Tissues (continued)

Neurons Develop from Epithelial Cells

Axon arises from “apical surface”; dendrites arise from “basolateral surface”.Plasmalemma: external cell membrane of a neuroncytoplasm = 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

Rough endoplasmic reticulum (rough ER)Smooth endoplasmic reticulum (smooth ER)Golgi apparatusNuclear envelopMitochondria (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

protein biosynthetic machinery (ribosomes, rough ER, Golgi complex).lysosomes

Axons are rich insynaptic vesiclesendocytic intermediates involved in synaptic vesicle trafficsynaptic 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.

Nucleus

Dendrite

ER

Golgi

Golgi

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.

Selective Distribution of Membranous Organelles in Neurons

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

axon

dendrite

The Cytoskeletal Structures of NeuronsThe 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

Microtubulessubunits: α- and β-tubulin25-28 nm in diameterpolar, dynamic structuretubulin 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 assemblyaxon: tau (causing microtubules to form tight bundles in axon) and MAP3dendrite: MAP2

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Expression of the Genes for Tau and MAP2C in a Nonneuronal Cell Line

Sf9 cells expressingtau protein

Sf9 cells expressingMAP2C proteinnormal Sf9 cells

Sf9 is an insect cell line that is non-neuronal.

Neurofilamentscytokeratin family including glial fibrillary acidic protein (GFAP)10 nm in diameterstable polymersneurofibrillary tangle in Alzheimer’s disease patients1 neurofilament 32 monomer

8 protofilaments in each neurofilament4 monomers in each protofilament

Microfilaments

subunits: β- and γ-actin monomer3-5 nm in diameterpolar, dynamic structureATPWith actin-binding proteins, actinfilaments 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.

dynamic, ∼ ½of the actin in neurons can be unpolymerized

3-5 nmATPβ-actinγ-actin (G)microfilament

stable and polymerized10 nmnone

cytokeratinsGFAP etc (F)

neurofilament

dynamic but more stable in mature axons and dendrites

25-28 nmGTPα-tubulinβ-tubulin (G)microtubule

The neurons that mediate the stretch reflex differ in morphology and

transmitter substanceSensory 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 enterthe spinal cord and

Green: dendrites of motorneurons

Fig. 4-8A: The axon of the sensory neuron bifurcates into a central and a peripheral branch. Sc, Schwann cells; Nuc, nucleolus; N, nucleus.

The sensory neuron conducts information from the periphery to the central nervous system

Fig. 4-8B: Motor neuron. Left, many dendritestypically 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 segmentAH: axon hillock

Motor neuron can receive signal inputs from…

Excitatory input from primary sensory neuronsRecurrent collateral branches of its ownRecurrent excitatory input from other motor neuronBoth excitatory and inhibitory input from interneurons driven by descending fibers from brain that control and coordinate movementInhibitory input from Renshaw cells (an interneuron in spinal cord using L-glycine as neurotransmitters)

The difference between sensory neurons and motor neurons

no dendritesL-glutamatepseudo-unipolarhas few if any boutonson its cell body; primary input from sensory receptors at the terminal of peripheral branch

extensive dendritic structuresacetylcholinemultipolarreceive 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 neuronConvergent- 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 neuronsMotor 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: basaldendrites (the same side that gives rise to axon) and apical dendritesThe 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 neuronsHippocampus (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.

Fig. 4-15 Pyramidal cells in theCA3 region of the hippocampus form synapses on the dendrites ofCA1 cells in the stratum radiatumLeft: Golgi-stained CA1pyramidal cells with dendrites extending downward 350 µm into stratum radiatum.Right: Three micrographs showsynapses formed on this CA1 cell by CA3 cells. A. Axons oftwo CA3 neurons form synapseson 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 formsynapses on two dendrites 263 µm from the cell body.

CA3

CA3

CA3

CA3

CA1

CA1 CA1

The spines on the CA1pyramidal cells have only excitatory synapse.

Four types of spinesin the dendrites of pyramidal cells in CA1region: thin, stubby,mushroom, branched.

The neck of the spine restricts diffusion between the head and the rest of dendrites. Each spine may functionas 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 myelinatingSchwann 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 diseasesThe 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 shiverermice, 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 over-production of this Schwann cell protein.

An Overall View

Four distinctive compartments in nerve cells

Cell body – protein synthesisAxon – projection over long distances to target cellsDendrites – receiving signal from other neuronsNerve terminals – release of neurotransmitters at synapses with targets