Cells of the CNS: Glia and Neurons

• Two big families: neurons and glia (non-neuronal cells). The three differentiated glia of the mature CNS are astrocytes, oligodendrocytes and microglia.
• Other cells you will meet: specialized (non-fenestrated) capillary endothelium + its basement ("basilar") membrane, and ependymal cells lining the ventricles.

• Why is white matter white? All that lipid-rich myelin (≈80% lipid).

• Non-neuronal: they do not fire action potentials.
• Have complex processes extending from the cell body (for contact and communication).
• Can divide and give rise to new glia (all three types proliferate) → contrast: mature neurons do not divide.
• Jobs: help define synaptic contacts, maintain neurons' signaling ability, maintain CNS homeostasis.

Astrocyte features

• Most abundant and largest glial cell; star-shaped ("astro").
• Can divide → astrogliosis (reactive proliferation).
• Protoplasmic (gray matter) have specialized endfeet; fibrous in white matter.
• Processes contact neuronal cell bodies, dendrites, axons, vessels and capillaries.
• One astrocyte can contact ~10⁵ synapses.
• Astrocytes produce glial fibrillary acidic protein (GFAP), an intermediate filament: the marker that identifies them.

The four big jobs: Grow, Guide, Guard, Govern

Astrocytes at the synapse

• Processes sit beside the synapse and take up released glutamate and GABA.
• Glutamate → glutamine (glutamine synthetase) → handed back to the neuron to remake transmitter.
• Have NT receptors (respond with Ca²⁺ rises), but no action potentials.

• Found in both gray and white matter; can divide.
• One oligodendrocyte myelinates several axons (one internode on each; up to dozens) ↔ a PNS Schwann cell myelinates one internode of one axon.
• Myelin = oligodendrocyte plasma membrane wrapped repeatedly and tightly around an axon segment (a myelin segment).
  • Protein + phospholipid with a high lipid:protein ratio (~80% lipid : 20% protein).
  • Contains proteins unique to CNS myelin, e.g., myelin basic protein (MBP), used as an identifier.
  • Insulates the axon → high resistance → impulses travel quickly.

CheckA section of gray matter shows oligodendrocytes clustered around neuron cell bodies. Are they making myelin?

No. Those are perineuronal oligodendrocytes: they hug cell bodies and are thought to support neurons with secreted molecules. Myelin comes from interfascicular (white-matter) oligodendrocytes.

CheckWhich protein is unique to CNS myelin and later becomes an autoimmune target?

Myelin basic protein (MBP).

• The sheath is not continuous: each myelinated stretch = an internode; the bare gap between = a node of Ranvier.
• Internode: insulated, high resistance, few channels → current flows down the axon instead of leaking out.
• Node: lower resistance, packed with voltage-gated Na⁺ channels → the action potential is regenerated here (K⁺ channels cluster nearby).
• The AP "leaps" node → node = saltatory conduction (Latin saltus, to leap).
• Payoff: faster and cheaper. Without myelin, channels (and Na⁺/K⁺-ATPase work) would be needed along the whole axon.

Microglia features

• Smallest glia; in both gray and white matter; can divide.
• The resident immune cells of the brain (macrophage-like).
• Actively migrate to monitor the CNS; survey for damage/infection and phagocytose debris.
• Hallmark: rapid activation in response to pathology.
• Surface receptors bind viral, bacterial and other pathogen molecules → activation.
• Development + plasticity: clear cells dying by normal programmed cell death and prune synapses throughout life.

Real activation is more complicated: there are likely additional subtypes and transition states between M1 and M2.

• Gliomas can arise from almost any glial cell (they can divide → can divide badly).
• Astrocytomas are the most common glial tumor.
  • Graded I–IV by degree of differentiation (better differentiated = lower grade).
• Glioblastoma (multiforme), GBM = malignant grade IV astrocytoma; poor survival.

Multiple sclerosis (MS)

• An idiopathic inflammatory demyelinating disease in which oligodendrocytes and myelin sheaths degenerate.

Progressive multifocal leukoencephalopathy (PML)

• A rare, fatal viral disease caused by the JC virus (human polyomavirus 2).
• The virus destroys oligodendrocytes → multifocal white-matter demyelination.
• Seen with immunosuppression (AIDS, natalizumab, rituximab).

Other cerebral injury that damages myelin

• Infarcts, infections, premature birth, hypoxia/ischemia, leukodystrophies.

This ties the whole cast together: neurons die first (highest metabolic demand), then neutrophils, microglia/macrophages clean up, and astrocytes scar.

• Main job: receive, process and send information.
• Structurally specialized for long-distance electrical signaling and communication via synapses.
• Scale: ~100 billion neurons, ~100 trillion synapses.
• Never work alone: organized into neural circuits that together produce behavior (movement, learning, memory). "Brain cells fire in patterns."
• Do not divide once mature and differentiated.
• Highly metabolically active: need lots of O₂, ATP and glucose.

• Neurons also have an extensive plasma membrane and a complex, specialized cytoskeleton (next question).

• Gives neurons their shape and makes function possible; it is dynamic: supports growth of processes, the polarized shape, and transport to and from the soma.
• Regulated by associated proteins, e.g., microtubule-associated proteins (MAPs).

• Extensions of the soma that are not myelinated; usually extensively branched ("tree-like").
  • Primary dendrites branch off the soma; secondary dendrites branch off those.
• Receive signals via postsynaptic receptors for neurotransmitters; information travels distal → proximal and converges on the soma.
• Dendritic spines = small protrusions.
  • Spine heads are the major site of postsynaptic ionotropic glutamate (excitatory) signaling.
  • Mature spines are mushroom-shaped (flat head, short shaft) → more surface for receptors.
  • Spine number and shape change with activity (plasticity).
• Clinical: autism is associated with more thin, immature spines → neurocognitive changes.

The soma is the support and metabolic center. Neurons make huge amounts of protein for a huge cell, so the soma looks like a factory:

• Arises from the soma at the axon hillock; ends at the axon terminal (presynaptic terminal).
  • Most neurons have a single axon.
  • The terminal is the site of small-molecule NT synthesis (e.g., ACh, glutamate, GABA, monoamines); neuropeptides are made in the soma and shipped down.
• Transmits information via action potentials (rapid change in charge across the axonal membrane) to other neurons or effector cells (e.g., muscle).
• Axoplasm: dense bundles of microtubules and neurofilaments (structure + transport of metabolites and organelles), smooth ER (lipid synthesis), mitochondria. No RER.
• Myelin: CNS axons by oligodendrocytes, PNS axons by Schwann cells; others unmyelinated. Myelin ↑ conduction (internodes, nodes rich in ion channels, saltatory conduction).

• Synapses let neurons work in circuits, transferring information neuron → neuron.
• Three parts: presynaptic element (axon terminal with vesicles, mitochondria) → synaptic cleft → postsynaptic element (neurotransmitter receptors).
• Postsynaptic contacts can be on dendrites (axodendritic), the cell body (axosomatic), along an axon or at axon terminals (axoaxonic). Many synapse types exist.
• Add the astrocyte process and you have the tripartite synapse (LO 1).

• Proteins (enzymes, receptors, neuropeptides) and organelles are made in the soma, yet the terminal may be up to a meter away.
• The terminal and dendrites also need to send signals and worn-out material back.
• So transport is critical for neuron function, is bidirectional and needs specialized motor proteins walking on microtubules.