Nervous Tissue

Open up the soma under high power and the first thing that strikes you is the nucleus. It is large, round, pale-staining, and carries one prominent nucleolus — the classic “vesicular nucleus” or “open-faced” nucleus. Why does it look so pale? Because the chromatin is largely euchromatic — the neuron is transcribing flat-out, day and night, to keep its huge cytoplasmic volume supplied with proteins. A cell with a long axon is essentially running a small factory shipping goods to a warehouse a metre away.

Around that nucleus sits the perikaryon, the cytoplasm of the cell body, and this is the home of two structures the examiner loves: Nissl bodies and neurofibrils. Nissl bodies are basophilic, tigroid-looking clumps that on EM resolve into stacks of rough endoplasmic reticulum studded with ribosomes, plus pools of free polyribosomes between the stacks. They are the protein-synthesis machinery of the neuron, and they are present in the perikaryon and in the dendrites — but they are conspicuously absent from the axon hillock and the axon. That single fact explains why the axon hillock stains pale and why the axon itself appears as a clear cable on light microscopy.

Neurofibrils are the second structure. With a silver stain they appear as fine brown filaments running through the soma, into the dendrites and right down the axon. On EM these “neurofibrils” are actually bundles of microtubules, microfilaments and neurofilaments — the cytoskeleton of the neuron. They give the cell its shape and they form the rails on which axonal transport runs, carrying vesicles forwards (anterograde) and recycled material backwards (retrograde) along the axon.

Dendrites and the axon may both be processes of the same neuron, but on histology and physiology they are nearly opposites. Dendrites are usually multiple, short, taper rapidly and branch like a tree. Their cytoplasm is essentially perikaryon stretched out — they still carry Nissl substance, mitochondria and Golgi — and many of them are studded with little knobs called dendritic spines where excitatory synapses land. Their job is to receive signals from many upstream neurons and pass that summed input into the soma.

The axon is the opposite. There is usually exactly one per neuron. It is long, thin, of uniform diameter, branches sparsely until it reaches its target, and arises from a specialised cone of cytoplasm called the axon hillock. The axon is wrapped in its own plasma membrane (axolemma) and its cytoplasm (axoplasm) contains neurofilaments, microtubules and mitochondria but, as we said, no Nissl bodies. Its job is to conduct the impulse away from the soma to the next cell, often over remarkable distances.

Because the axon has no ribosomes, every protein it needs — from vesicle membranes to ion-channel subunits to the housekeeping enzymes at the terminal — has to be manufactured in the soma and trucked down the axon. That is what axonal transport does. Anterograde transport (soma → terminal) is driven by kinesin motors walking along microtubules, carrying vesicles full of neurotransmitter and membrane. Retrograde transport (terminal → soma) is driven by dynein, recycling membrane and returning growth signals — but, as the rabies and herpes viruses have learned to exploit, also unwelcome cargo.

• Dendrites: usually multiple, branched; cytoplasm similar to perikaryon (contain Nissl); bear dendritic spines; receive stimuli.
• Axon: usually one, long, thin, few branches; arises at the axon hillock; covered by axolemma; axoplasm has neurofibrils & mitochondria but no Nissl bodies; conducts impulses away from the soma.
• Axonal transport: anterograde (soma→terminal, kinesin) & retrograde (terminal→soma, dynein) — exploited by rabies, tetanus and herpes.

This is the one structure in the whole unit you can almost guarantee will appear as a long-essay question. So learn it as a story rather than as a list. Start at the centre and work outwards. In the middle of every PNS myelinated fibre is an axon — the actual conductor. Wrapped tightly around that axon is the myelin sheath, made from the plasma membrane of a single Schwann cell that has rolled itself around the axon dozens of times to produce a compact spiral of lipid. The Schwann-cell nucleus and the thin rim of cytoplasm that contains it sit on the outside of the sheath and form the neurolemma.

Now run your eye along the fibre. The Schwann cells line up like beads on a string, and where two adjacent Schwann cells meet there is a tiny unmyelinated gap a micron or so wide called the node of Ranvier. At the node the axolemma is exposed and densely packed with voltage-gated Na⁺ channels — this is where the action potential is regenerated. The length of myelinated axon between two nodes (one Schwann cell’s worth) is the internode. Inside the myelin you will sometimes see oblique pale clefts; these are Schmidt-Lanterman incisures, small pockets of Schwann-cell cytoplasm trapped inside the spiral that keep the sheath supplied and flexible. The narrow connection from the outer cytoplasm into the spiral is called the mesaxon.

All of this anatomy exists for one reason: saltatory conduction. Because myelin is a great electrical insulator, the impulse cannot leak out along the internode; it can only regenerate at the next node. So it appears to leap from node to node, vastly faster than a continuous wave would travel. Strip the myelin and conduction collapses — which is exactly what happens in multiple sclerosis and in Guillain-Barré.

A quick note on the CNS counterpart and on unmyelinated fibres, because the contrast is high-yield. In the CNS the myelin is made by an oligodendrocyte — one oligodendrocyte myelinates several different axons, there is no neurolemma, no basal lamina, and the cell body sits in the parenchyma rather than against the axon. In the PNS, unmyelinated fibres are not bare; instead, one Schwann cell wraps itself loosely around several thin axons, parking each one in a groove on its surface. This bundle is sometimes called a Remak bundle. No spiral, no compact myelin, no nodes, no saltatory conduction — just slow continuous conduction.

• Axon: in the centre.
• Myelin sheath: at the periphery, formed by the wrapped plasma membrane of a Schwann cell (lipid + protein); neurolemma = outer Schwann-cell cytoplasm + nucleus.
• Node of Ranvier: the narrow gap between adjacent Schwann cells where the axolemma is exposed; densely packed with Na⁺ channels.
• Internode: the myelinated segment between two nodes (= one Schwann cell).
• Schmidt-Lanterman incisures: small clefts of Schwann-cell cytoplasm within the myelin, giving flexibility & aiding turnover.
• Mesaxon: the membrane connection between the outer Schwann-cell surface and the start of the myelin spiral.
• Function: insulation + saltatory conduction (impulse jumps node-to-node → faster).

A peripheral nerve is not a single fibre — it is hundreds or thousands of fibres bound together in connective tissue. Histology gives you three concentric wrappings, and on a transverse section you can name all three by where you find them. Innermost is the endoneurium, a delicate layer of reticular fibres and a basal lamina that hugs each individual nerve fibre (one axon plus its Schwann cells). A group of these fibres is bundled into a fascicle by a tougher, layered sleeve of flattened epithelioid cells called the perineurium — and the perineurium does something special: its tight junctions form the blood-nerve barrier, the peripheral analogue of the BBB. Several fascicles are then bundled together by a thick dense-irregular outer coat called the epineurium, which carries the larger blood vessels of the nerve (vasa nervorum) and gives the nerve its mechanical strength.

A second high-yield piece of nerve histology is the ganglion. A ganglion is a cluster of neuronal cell bodies in the PNS, and you must be able to tell two kinds apart. The sensory ganglion (dorsal root ganglion of a spinal nerve, or a sensory cranial ganglion) holds round pseudounipolar cell bodies, neatly arranged with satellite cells around each one, and no synapses inside. The autonomic ganglion holds multipolar cell bodies, scattered rather than arranged, with eccentric nuclei, fewer satellite cells — and synapses do occur inside (this is where preganglionic fibres terminate). Grey matter of the brain is not called a ganglion (basal ganglia are an old-school exception); proper ganglia are PNS structures.