Nervous Tissue Histology & Glial Cells

Nervous tissue is built from two cardinal cell populations: neurons (excitable, conducting units) and neuroglia (supporting, non-conducting cells that vastly outnumber neurons). This note maps the perikaryon, axon and myelin in fine histological detail, contrasts CNS versus PNS glia, and links it all to the degeneration–regeneration phenomena that NEET PG loves to test.

Overview & classification

Nervous tissue arises almost entirely from neuroectoderm (the neural tube and neural crest), with the notable exception of microglia, which are of mesodermal (yolk-sac monocyte) origin. Functionally, the tissue is organised into the central nervous system (CNS) — brain and spinal cord — and the peripheral nervous system (PNS) — cranial/spinal nerves and ganglia.

Neuron classification:

Basis	Types	Example
Number of processes	Unipolar (pseudounipolar), bipolar, multipolar	Pseudounipolar → dorsal root ganglion; Bipolar → retina, olfactory, cochlear/vestibular ganglia; Multipolar → motor neurons, pyramidal cells
Function	Sensory (afferent), motor (efferent), interneuron	Most CNS neurons are interneurons
Axon length	Golgi type I (long axon) vs Golgi type II (short axon)	Type I → pyramidal/Purkinje; Type II → local circuit

High-yield: Bipolar neurons are found in the retina, olfactory epithelium, and the cochlear & vestibular (spiral & Schwann's) ganglia. Pseudounipolar neurons are characteristic of the dorsal root ganglion and the mesencephalic nucleus of trigeminal (the only CNS-located primary sensory neuron cell bodies).

The neuron: perikaryon & organelles

The perikaryon (soma/cell body) contains the nucleus and the bulk of synthetic machinery. Classic histological signatures:

• Nissl bodies (Nissl substance): clumps of rough endoplasmic reticulum + free polyribosomes, basophilic on H&E and intensely stained by basic aniline dyes (cresyl violet, toluidine blue). They reflect high protein synthesis. Large motor neurons show coarse "tigroid" Nissl; smaller neurons show fine granules.
• Nucleus: large, central, vesicular (euchromatic) with a prominent nucleolus — an "owl's eye" appearance. In females, a Barr body may sit against the nucleolus ("nucleolar satellite").
• Neurofibrils: bundles of neurofilaments (intermediate filaments) + microtubules, demonstrated by silver staining; provide cytoskeletal scaffolding and axonal transport rails.
• Golgi apparatus, mitochondria, lysosomes, lipofuscin (wear-and-tear pigment accumulating with age) and neuromelanin (in substantia nigra and locus coeruleus).

High-yield: Nissl bodies are ABSENT from the axon hillock and the axon, but PRESENT in the dendrites. This is the single most repeated histology MCQ for neurons. The axon hillock is the trigger zone for the action potential and the lowest-threshold region (highest density of voltage-gated Na⁺ channels at the adjoining initial segment).

Dendrites vs axon — quick contrast

Feature	Dendrite	Axon
Number	Usually multiple	Single per neuron
Nissl bodies	Present	Absent
Branching	Profuse, near soma	Collaterals at right angles, distal terminal arbor
Diameter	Tapers	Uniform
Direction of conduction	Towards soma (afferent)	Away from soma (efferent)
Spines/Boutons	Dendritic spines	Terminal boutons

Axonal transport flow: Anterograde (kinesin, towards terminal) → fast (~400 mm/day, organelles/vesicles) + slow (cytoskeleton); retrograde (dynein, towards soma) → recycled material, trophic signals, and unfortunately also rabies, tetanus toxin, polio & herpes viruses.

Neuroglia of the CNS

Glia outnumber neurons roughly 10:1 and do not generate action potentials. CNS glia:

Cell	Origin	Stain/feature	Key functions
Astrocyte	Neuroectoderm	GFAP positive	Blood–brain barrier (foot processes), K⁺ buffering, glutamate uptake, glial scar (astrogliosis), metabolic support
Oligodendrocyte	Neuroectoderm	Few processes	Myelination in CNS — one cell myelinates up to ~50 axon segments
Microglia	Mesoderm (yolk sac monocytes)	Smallest glia	Resident phagocytes/macrophages, antigen presentation, become "gitter cells"
Ependymal cells	Neuroectoderm	Ciliated columnar	Line ventricles & central canal; tanycytes and choroid plexus (CSF production)

Astrocyte subtypes: Protoplasmic astrocytes in grey matter (many short branched processes); Fibrous astrocytes in white matter (long, slender, GFAP-rich processes). Both contact capillaries via perivascular end-feet, the structural basis of the blood–brain barrier alongside tight-junctioned endothelium.

High-yield: The most reliable immunohistochemical marker for astrocytes is GFAP (glial fibrillary acidic protein). GFAP positivity is also used to grade astrocytomas. Microglia are CD68/Iba1 positive and are the ONLY neural-tissue cells of mesodermal origin.

High-yield: In the CNS, one oligodendrocyte myelinates multiple (many) axons; in the PNS, one Schwann cell myelinates only a single internode of one axon. This reciprocal relationship is a perennial favourite.

Neuroglia / support of the PNS

• Schwann cells (neurolemmocytes): myelinate PNS axons; one Schwann cell = one internode. Form the neurilemma (sheath of Schwann), essential for regeneration. Unmyelinated PNS axons are still enveloped (multiple axons in one Schwann cell's invaginations → "Remak bundle").
• Satellite cells: surround neuronal cell bodies in sensory and autonomic ganglia; analogous to astrocytes, provide insulation and metabolic exchange.

Myelin sheath — structure & formation

Myelin is a lipid-rich (≈70–80% lipid), multilamellar wrapping of the plasma membrane of the myelinating glial cell. It increases conduction velocity by enabling saltatory conduction.

Key landmarks:

• Nodes of Ranvier: unmyelinated gaps with dense voltage-gated Na⁺ channels; site of impulse "jump."
• Internode: myelinated segment between two nodes (one Schwann cell in PNS).
• Schmidt–Lanterman incisures (clefts): islands of Schwann-cell cytoplasm within the myelin — present in PNS, essentially absent/rare in CNS.
• Mesaxon: the doubled membrane formed as the glial cell wraps around the axon.

High-yield: Major dense line = fusion of the inner (cytoplasmic) leaflets of the membrane; Intraperiod (minor dense) line = apposition of the outer (extracellular) leaflets. This electron-microscopy detail is repeatedly asked.

Major myelin proteins: PNS myelin is rich in P0 (protein zero, ~50%) and PMP22 (mutated/duplicated in Charcot–Marie–Tooth disease type 1A); CNS myelin is rich in proteolipid protein (PLP) and myelin basic protein (MBP) — MBP is the key autoantigen implicated in multiple sclerosis.

Feature	CNS myelin (oligodendrocyte)	PNS myelin (Schwann cell)
Cell : axon ratio	1 oligodendrocyte : many axons	1 Schwann cell : 1 internode
Neurilemma (outer cytoplasmic sheath)	Absent	Present
Basal lamina	Absent	Present
Schmidt–Lanterman incisures	Rare/absent	Present
Key proteins	PLP, MBP	P0, PMP22
Regeneration capacity	Poor	Good
Demyelinating disease	Multiple sclerosis, PML	Guillain–Barré syndrome, CMT

Degeneration: Wallerian degeneration & chromatolysis

When a peripheral nerve axon is severed, two coordinated changes occur — one distal to the injury and one in the soma.

Wallerian (anterograde) degeneration — distal to the cut:

1. The axon distal to the injury, deprived of its soma, disintegrates (the axon and its myelin break up).
2. Myelin fragments into ovoids; Schwann cells and macrophages phagocytose the debris (Schwann cells proliferate).
3. Surviving Schwann cells line up within their persisting basal lamina to form bands of Büngner, which guide the regenerating axon.

Chromatolysis (the axon reaction / retrograde change in the soma):

• Dispersal/dissolution of Nissl substance (loss of basophilia), beginning centrally.
• Swelling of the cell body and eccentric (peripheral) displacement of the nucleus.
• This reflects a switch from neurotransmitter synthesis to structural protein synthesis for repair.

High-yield: The histological triad of chromatolysis = (1) central chromatolysis (loss of Nissl), (2) cell-body swelling, (3) eccentric/peripheral nucleus. It indicates an attempt at regeneration, not death.

Transneuronal (transsynaptic) degeneration: degeneration that spreads to the next neuron in the pathway (e.g., lateral geniculate body neurons after retinal/optic nerve loss).

Regeneration

Aspect	PNS	CNS
Regeneration	Occurs (Schwann tube + bands of Büngner guide regrowth)	Largely fails
Growth rate	~1 mm/day (≈1 inch/month)	—
Inhibitory factors	Few	Nogo, MAG, OMgp; glial scar (astrocytes)
Guiding structure	Basal lamina + bands of Büngner	Absent

PNS regeneration flow: Wallerian degeneration distal to cut → Schwann cells proliferate within intact basal lamina → bands of Büngner form → proximal axon sprouts a growth cone → axon advances ~1 mm/day along the band → re-myelination & target re-innervation.

High-yield: Successful PNS regeneration depends on the intact endoneurial tube/basal lamina and the neurilemma (Schwann sheath). If proximal and distal stumps are misaligned or separated, axons sprout chaotically → traumatic (amputation) neuroma. CNS neurons fail to regenerate chiefly because of the inhibitory glial scar and myelin-associated inhibitors (Nogo-A).

Seddon classification of nerve injury (clinically tested alongside histology):

Grade (Seddon)	Sunderland	Lesion	Wallerian degeneration	Recovery
Neurapraxia	I	Focal demyelination, axon intact	No	Full, rapid (days–weeks)
Axonotmesis	II–IV	Axon severed, connective sheaths variably intact	Yes	Good if endoneurium intact
Neurotmesis	V	Complete transection (axon + sheaths)	Yes	Poor; needs surgery

Special histology pearls

• Cerebellar Purkinje cells: large, flask-shaped multipolar neurons with a single, extensively branched dendritic tree confined to a single plane — a classic Golgi type I neuron.
• Pyramidal cells of the cerebral cortex: triangular soma with an apical dendrite.
• Renshaw cells (spinal interneurons), basket cells and granule cells of cerebellum are common naming MCQs.
• Choroid plexus = modified ependyma + fenestrated capillaries → produces CSF; site of the blood–CSF barrier (tight junctions are at the epithelium, not the endothelium here).

High-yield: The blood–brain barrier tight junctions are in the capillary endothelium (astrocyte foot processes are supportive). In the choroid plexus (blood–CSF barrier) the tight junctions are at the ependymal/epithelial layer because the capillaries there are fenestrated. Distinguishing the two is a frequent trap.

Mnemonics

• Nissl in axon? "NO Nissl in the hillock or axon." (N for No, N for Nissl.)
• Bipolar neuron sites — "ROCC": Retina, Olfactory, Cochlear, Crista/vestibular (and the spiral & vestibular ganglia).
• CNS regeneration blockers — "MON": MAG, OMgp, Nogo.
• PNS myelin protein — "P-zero for Peripheral."
• Chromatolysis = "Swollen body, Eccentric nucleus, Faded Nissl" (SEF).

Recently asked / exam angle

• EM appearance of myelin — identify the major dense line (inner leaflet fusion) versus the intraperiod line (outer leaflet apposition).
• "Which structure is absent in the axon?" → Nissl substance / rough ER (also no Golgi-based protein synthesis machinery in the distal axon).
• One oligodendrocyte myelinates how many axons? → multiple; one Schwann cell → one internode.
• Chromatolysis features and significance — eccentric nucleus + Nissl dispersal = regenerative axon reaction, classically paired with a clinical motor-neuron injury vignette.
• Bands of Büngner — what do they do? → guide regenerating axons in the PNS.
• GFAP as the astrocyte marker; microglia origin = mesoderm (the odd one out among neural cells).
• PMP22 duplication → CMT 1A; P0 in PNS myelin; MBP/PLP in CNS.
• Rate of peripheral nerve regeneration ≈ 1 mm/day — used to estimate recovery time in nerve-injury vignettes.
• Schmidt–Lanterman incisures present in PNS — "which is a feature of peripheral myelin?"
• Blood–CSF barrier site = choroid plexus epithelium tight junctions.

Rapid revision

1. Nissl bodies = rough ER + polyribosomes; present in soma & dendrites, absent in axon hillock and axon.
2. Axon hillock/initial segment = action-potential trigger zone (dense Na⁺ channels).
3. One oligodendrocyte → many CNS axons; one Schwann cell → one PNS internode.
4. Microglia are mesodermal (yolk-sac monocytes); all other neural cells are neuroectodermal.
5. GFAP = astrocyte marker; protoplasmic (grey matter) vs fibrous (white matter) astrocytes.
6. Major dense line = inner (cytoplasmic) leaflet fusion; intraperiod line = outer leaflet apposition.
7. Schmidt–Lanterman incisures & neurilemma = PNS only.
8. PNS myelin → P0 & PMP22; CNS myelin → PLP & MBP.
9. Wallerian degeneration = breakdown distal to a cut; bands of Büngner guide PNS regrowth.
10. Chromatolysis = central Nissl dispersal + swollen soma + eccentric nucleus = regenerative reaction.
11. PNS regenerates (~1 mm/day); CNS fails due to glial scar + Nogo/MAG/OMgp.
12. Bipolar neurons → retina, olfactory, cochlear & vestibular ganglia; pseudounipolar → dorsal root ganglion.