Under a microscope, nervous tissue looks like a dense, tangled network of large cells with long branching extensions, surrounded by smaller supporting cells. The exact appearance depends on the stain used and whether you’re looking at brain tissue, spinal cord, or a peripheral nerve, but the defining feature is always the neuron: a large cell body with a pale, round nucleus and dark-staining granules in its cytoplasm, with processes extending outward in multiple directions.
The Neuron Cell Body Up Close
The cell body, or soma, is the most recognizable part of a neuron in a stained tissue section. Its nucleus is large, round, and notably pale compared to other cell types because the DNA is loosely packed. Inside that pale nucleus sits a single dark dot, the nucleolus, which is so prominent that histologists sometimes describe the whole arrangement as an “owl-eye” or “fried-egg” nucleus. This look is distinctive enough that you can often pick out neurons at a glance, even at low magnification.
The cytoplasm surrounding the nucleus appears grainy or mottled. That texture comes from Nissl bodies, which are dense clusters of protein-making machinery (rough endoplasmic reticulum and ribosomes). They stain intensely blue or purple with most dyes and fill the cytoplasm in irregular clumps. Nissl bodies are a reliable identifier: almost no other cell type has cytoplasm that looks this rough and darkly stained.
Dendrites, Axons, and the Axon Hillock
Several thick processes called dendrites extend from the cell body. Near the soma, dendrites are broad and still contain Nissl bodies, so they stain dark at their base. As they branch farther away, they get thinner and lose that dark staining, eventually becoming so fine that they disappear into the background of the slide. In a standard tissue preparation, you typically can’t see the full branching tree of a neuron’s dendrites.
The axon leaves the cell body at a region called the axon hillock. Under the microscope, the hillock stands out because it lacks Nissl bodies entirely, making that patch of cytoplasm look pale and clear compared to the rest of the soma. This absence is one of the few ways to tell an axon apart from a dendrite in a routine slide, though it isn’t always easy to spot.
How Different Stains Change What You See
The appearance of nervous tissue shifts dramatically depending on the staining method. The most common stain in histology, hematoxylin and eosin (H&E), turns nuclei and ribosomes blue-purple while coloring the surrounding cytoplasm and connective tissue pink. With H&E, neurons show blue-purple nuclei and a pinkish cell body speckled with blue-purple Nissl clumps.
Nissl staining (also called cresyl violet) is specifically designed for nervous tissue. It uses a basic dye that binds tightly to the ribosomal RNA in Nissl bodies, making neuron cytoplasm appear dark blue while leaving supporting cells mostly unstained. This makes it easy to map where neurons are concentrated in brain and spinal cord sections without the visual clutter of other cell types.
The Golgi stain produces the most dramatic images. It deposits silver into a random subset of neurons, turning them completely black against a clear, pale background. Because the tissue sections are cut thick (over 100 micrometers), you can trace the entire three-dimensional silhouette of a neuron: its soma, its full dendritic tree, and its axon. The Golgi-Cox variation is considered the best method for revealing entire dendritic trees of cortical neurons, producing very dark dendrites against an almost transparent background. Most of the classic drawings of neuron shapes you see in textbooks were originally traced from Golgi-stained preparations.
Recognizable Neuron Shapes
Not all neurons look the same. Two types are especially easy to identify because of their distinctive shapes.
Pyramidal neurons, found throughout the cerebral cortex, have a triangular cell body with a single thick dendrite extending upward toward the brain’s surface and several smaller dendrites branching from the base. That triangle-plus-apical-dendrite shape is unmistakable, and these cells appear in every cortical layer except the outermost one.
Purkinje cells in the cerebellum are even more striking. They have a large, flat cell body with an enormous, highly branched dendritic tree that fans out in a single plane, like a coral or a bare winter tree. The dendritic tree is oriented perpendicular to the folds of the cerebellar surface, so when the tissue is cut in the right plane, the full fan shape is visible. A single long axon extends from the opposite side of the cell body.
Gray Matter Versus White Matter
At low magnification, nervous tissue in the brain and spinal cord divides into two visually distinct zones. Gray matter is packed with neuron cell bodies, supporting cells, and unmyelinated dendrites. It looks dense and cellular, with many visible nuclei. Despite the name, in a stained section it actually appears relatively pale because it lacks the fatty myelin coating found on many nerve fibers.
White matter, by contrast, contains no neuron cell bodies. It’s made up almost entirely of myelinated nerve fibers running in bundles. In cross section, these fibers look like tiny rings or donuts: a pale center (the axon) surrounded by a dark ring (the myelin sheath). In a spinal cord cross section, the butterfly-shaped gray matter in the center is surrounded by white matter on the outside, and the difference in texture between the two is immediately obvious.
Peripheral Nerves in Cross Section
A peripheral nerve, like the one running down your arm, looks quite different from brain tissue. Cut in cross section, it resembles a cable made of smaller cables. The entire nerve is wrapped in a thick layer of dense connective tissue called the epineurium. Inside that, bundles of individual nerve fibers (fascicles) are each wrapped in their own sheath, the perineurium. And within each fascicle, every single nerve fiber has a thin layer of connective tissue around it, the endoneurium.
The individual nerve fibers within each fascicle appear as small circles. Myelinated fibers show the characteristic ring pattern: a dark-staining myelin sheath surrounding the lighter axon in the center. With a toluidine blue stain, the myelin rings stand out in deep blue. If you look at a longitudinal section instead of a cross section, the myelin sheath appears as two parallel dark lines running along either side of the axon, with periodic gaps where the sheath of one supporting cell ends and another begins.
Supporting Cells and How to Tell Them Apart
Neurons make up a minority of cells in nervous tissue. The majority are glial cells, or neuroglia, which are smaller and harder to distinguish from one another in routine preparations. Astrocytes are the largest glial cells, with many fine processes radiating outward that give them a star-shaped appearance when stained with silver. Oligodendrocytes are smaller, with fewer and shorter processes. Microglia are the smallest, with elongated cell bodies and irregular, thorny branches.
In a standard H&E or Nissl-stained section, glial cells mostly appear as small, dark nuclei scattered between neurons. You can’t reliably tell one type from another without special stains or silver impregnation techniques. The Nissl stain is useful here because it specifically highlights neuron cytoplasm while leaving astrocyte cell bodies largely unstained, making it easier to count and locate neurons.
What Electron Microscopy Reveals
Light microscopy can show cell bodies, dendrites, and myelin sheaths, but the finest details of nervous tissue only become visible with electron microscopy, which magnifies structures thousands of times more. At this level, the synapse (the junction between two neurons) becomes visible as two closely opposed membranes separated by a tiny gap roughly 180 to 300 angstroms wide, far too small for any light microscope to resolve.
The presynaptic terminal, the part of the neuron sending a signal, is filled with small round spheres called synaptic vesicles, each about 200 to 650 angstroms in diameter. These vesicles contain the chemical messengers that carry signals across the gap. Mitochondria and fine filaments are also visible in the terminal. The myelin sheath, which looks like a single dark ring under a light microscope, resolves into dozens of tightly wrapped concentric layers when viewed with an electron microscope, like a rolled-up sheet of membrane spiraling around the axon.