Pyramidal cells

Structure of the cerebral cortex

The isocortex consists of six layers, numbered from the surface inwards:

• I Molecular layer: few cells, mainly fibres and dendrites
• II External granular layer: small granule and pyramidal cells
• III External pyramidal layer: medium-sized pyramidal cells
• IV Internal granular layer: granule cells, input from the thalamus
• V Internal pyramidal layer: large pyramidal cells, including the giant Betz cells of the motor cortex
• VI Multiform layer: cells of varied shape

The white matter lies beneath. The layer boundaries are indistinct and are hard to define reliably on H&E sections without practice.

Pyramidal cell and neuropil

The soma of a pyramidal cell contains a large, pale (euchromatic) nucleus with a prominent nucleolus and abundant basophilic Nissl substance (rough ER). The axons of pyramidal cells form the main projection pathways of the cortex: to other cortical areas, to the opposite hemisphere via the corpus callosum and to the brainstem and spinal cord (pyramidal tract). Between the neurons lies the neuropil, a fine meshwork of dendrites, axons and glial processes. In it you can see small, dark glial nuclei without visible cytoplasm, as well as capillaries. Their continuous endothelium with tight junctions, together with the basal lamina and astrocytic end-feet, forms the blood–brain barrier.

Microscopy tips

Start at low power and find the brain surface with the pia mater – this tells you which direction the apical dendrites should point. Then switch to high power: pyramidal cells are recognised by their triangular soma, a large pale nucleus with a nucleolus and a thick process at the apex. Glial nuclei are much smaller, round or elongated and darker. Clear spaces around neurons and vessels are usually shrinkage artefacts. Very dark, shrunken neurons (“dark neurons”) are often caused by tissue handling. Differential: cerebellar Purkinje cells lie in a row above a dense granular layer; spinal motor neurons are larger, polygonal and have coarse Nissl bodies.

Clinical relevance

Large pyramidal cells in layers III and V are particularly vulnerable to hypoxia. After a hypoxic insult they appear as “red neurons” with eosinophilic cytoplasm and a shrunken, dark nucleus. In amyotrophic lateral sclerosis the Betz cells of the motor cortex and the spinal motor neurons degenerate. In Alzheimer’s disease, pyramidal cells of the hippocampus and association cortex in particular lose their synapses and die. Damage to the pyramidal tract causes upper motor neuron paralysis with brisk reflexes and a positive Babinski sign.

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