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Histology of the Nervous System

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Overview

• Central Nervous System (CNS) — brain and spinal cord
• Peripheral Nervous System (PNS) — all nerves, ganglia, and sensory receptors outside the CNS

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PART 1: THE NEURON

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1.1 Classification of Neurons

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1.2 The Cell Body (Perikaryon/Soma)

• Large, pale-staining (euchromatic) — reflects active gene transcription
• Prominent nucleolus — active ribosomal RNA synthesis
• Usually centrally placed (exception: dorsal root ganglion neurons have eccentric nuclei)

Key exam point: Nissl bodies are absent in the axon hillock and in the axon itself, but are present in dendrites.

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1.3 Dendrites

• Receptor processes that receive stimuli from other neurons or the environment and transmit them toward the cell body
• Usually short, tapered, extensively branched — form dendritic trees that greatly increase receptor surface area
• Unmyelinated
• Contain rER, free ribosomes, small Golgi outposts, microtubules
• Many CNS neurons have dendritic spines — small protrusions (actin-based) involved in synaptic plasticity, learning, and memory
  • Mushroom-shaped spines = mature spines (~70–80% of total)
  • Contain postsynaptic density

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1.4 The Axon

• Usually a single, long process; transmits impulses away from the cell body to synaptic terminals
• Begins at the axon hillock — a cone-shaped elevation of the cell body where action potentials are initiated
• Lacks Nissl bodies and has sparse rER
• May be myelinated or unmyelinated
• Axolemma = plasma membrane of the axon
• Axoplasm = cytoplasm of the axon

• Enlarged tips that form synapses
• Contain synaptic vesicles filled with neurotransmitter
• Contact points along the axon are called boutons en passant; terminal enlargements are boutons terminaux

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1.5 Synapses

• Presynaptic membrane — contains synaptic vesicles with neurotransmitter
• Synaptic cleft — ~20–30 nm wide
• Postsynaptic membrane — contains receptors; shows postsynaptic density (electron-dense thickening)

Synapses are not visible in routine H&E staining. They require silver precipitation (Golgi method) or electron microscopy.

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PART 2: NEUROGLIA (GLIAL CELLS)

2.1 CNS Neuroglia

A. Astrocytes

• Largest glial cells in the CNS
• Two types:
  • Protoplasmic astrocytes — found in grey matter; short, thick, branching processes
  • Fibrous astrocytes — found in white matter; long, slender, unbranched processes containing GFAP (glial fibrillary acidic protein)
• Marker: GFAP (glial fibrillary acidic protein) — used for immunohistochemical identification
• Functions:
  • Structural support (form glial limitans at CNS surface)
  • Form perivascular end-feet around blood vessels → contribute to blood-brain barrier (BBB)
  • Regulate extracellular K⁺ and glutamate concentrations
  • Nutritional support for neurons
  • Form glial scar (gliosis) after CNS injury

B. Oligodendrocytes

• Smaller than astrocytes; fewer, shorter processes
• Function: Produce and maintain myelin sheath in the CNS
• A single oligodendrocyte myelinates multiple axons (up to 50)
• Identified by small, round, dense nucleus; sparse cytoplasm
• Analogous to Schwann cells in the PNS
• Target in multiple sclerosis (demyelinating disease)

C. Microglia

• Smallest glial cells; elongated, dense, irregular nuclei with many short processes
• Derived from monocytes (bone marrow) — the only glial cells of non-neural origin
• Function: CNS's resident macrophages — phagocytose debris, dead cells, pathogens
• Become activated (ameboid) after CNS injury → transform into phagocytes
• Marker: CD68, Iba-1

D. Ependymal Cells

• Simple cuboidal to columnar epithelium lining the ventricular system (brain ventricles and central canal of spinal cord)
• Some bear cilia (beat CSF) and microvilli
• Specialized ependymal cells:
  • Choroid plexus cells — modified ependymal cells that produce cerebrospinal fluid (CSF)
  • Tanycytes — contact portal vessels; link CSF to hypothalamic neurons

2.2 PNS Supporting Cells

A. Schwann Cells (Neurilemma Cells)

• Analogous to oligodendrocytes but each Schwann cell myelinates only one axon segment
• Wrap concentrically around the axon to form the myelin sheath
• Myelinated fibers:
  • Gaps in myelin at regular intervals = Nodes of Ranvier → allow saltatory conduction
  • Oblique cytoplasmic channels in myelin = Schmidt-Lanterman clefts (incisures) — allow metabolite exchange; number correlates with axon diameter
  • The outer collar of Schwann cell cytoplasm forms neurolemma (neurilemma) — important for PNS nerve regeneration
• Unmyelinated fibers (Remak Schwann cells):
  • A single Schwann cell envelops multiple small-diameter axons in surface grooves
  • Grooves may be open (mesaxon exposed) or closed (forming a mesaxon)
• Marker: S-100 protein

B. Satellite Cells

• Small, flat cells surrounding neuron cell bodies in ganglia
• Provide structural and metabolic support to ganglionic neurons
• Analogous to astrocytes in function

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PART 3: NERVE FIBERS

3.1 Myelinated Nerve Fibers (PNS)

• Each internode = one Schwann cell wrapped around one axon segment
• Node of Ranvier = bare axon between two internodes (~1 µm wide)
• Myelin composition: ~70–80% lipid (cholesterol, phospholipids, sphingomyelin), ~20–30% protein (MBP, PLP)
• In cross-section (EM): myelin appears as concentric dark and light lamellae
• In light microscopy: myelin dissolves in routine processing (lipid solvents) → appears as empty space

3.2 Classification of Nerve Fibers

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PART 4: CONNECTIVE TISSUE SHEATHS OF PERIPHERAL NERVES

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PART 5: GANGLIA

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PART 6: CNS TISSUE ORGANIZATION

Grey Matter vs. White Matter

Blood-Brain Barrier (BBB)

• Formed by: tight junctions between CNS endothelial cells + astrocyte perivascular end-feet + pericytes + basement membrane
• Restricts passage of large molecules, pathogens, and most drugs into brain
• Absent in circumventricular organs (area postrema, median eminence, neurohypophysis)

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PART 7: KEY STAINING METHODS

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PART 8: NEURAL REGENERATION

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Quick Revision Summary

NEURONS:
  Cell body (perikaryon) → Nucleus + Nissl bodies (rER) + organelles
  Dendrites → receive signals → contain Nissl substance
  Axon → transmit signals away → NO Nissl bodies (absent from hillock onward)
  Synapse → axodendritic (most common), axosomatic, axoaxonic

NEUROGLIA (CNS):
  Astrocytes → BBB, support, GFAP+
  Oligodendrocytes → CNS myelin (one cell, many axons)
  Microglia → phagocytes (monocyte origin), CD68+
  Ependymal cells → line ventricles; choroid plexus → CSF

PNS SUPPORT:
  Schwann cells → PNS myelin (one cell, ONE axon segment) + S-100+
  Satellite cells → surround ganglionic neurons

NERVE SHEATHS: Endoneurium → Perineurium → Epineurium

GREY vs WHITE MATTER:
  Grey → cell bodies + neuropil
  White → myelinated axons only

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