EM 398 Pyramidal Neuron

Pyramidal Neuron

Transmission electron microscopy (TEM) of a pyramidal neuron in the prefrontal cortex of a 5-year-old monkey.

Pyramidal neurons are the most abundant and functionally important cells in the cerebral cortex. They are the primary excitatory neurons responsible for cognitive processing, memory formation, and integrating information across cortical regions. Their distinctive pyramid-shaped cell bodies and elaborate dendritic trees allow them to receive and process input from large numbers of neurons,

Fundamental Neuronal Architecture

All neurons share a basic structural organization optimized for intercellular signaling:

• Cell Body (Soma): Contains the nucleus and most organelles; center of metabolic activity
• Dendrites: Branching input structures that receive signals from other neurons
• Axon: Single output fiber that transmits signals to target cells
• Axon Terminals: Specialized endings that form synaptic connections
• Synapses: Precise junctions enabling cell-to-cell communication

Neuropil

The space surrounding neurons, known as the neuropil, consists of densely packed neuronal elements (dendrites, axons, and synapses), glial cells and their processes, and blood vessels.

Structure and Function

The following pages discuss these elements in more detail.

Courtesy of Alan Peters and Claire Folger Sethares, The Fine Structure of the Aging Brain ((www.bu.edu/agingbrain), Boston University School of Medicine, Boston, MA.

Cell Body (Soma)

The cell body, often called the soma, of pyramidal neurons, exhibits a distinctive pyramidal shape containing the nucleus surrounded by the cellular machinery necessary for its demanding metabolic requirements.

Nucleus:

• Nucleus (blue): Large, centrally located with dispersed chromatin (euchromatin), indicating active transcription
• Nuclear Envelope (purple): Double membrane system regulating molecular transport between the nucleus and cytoplasm
• Nucleoli: Prominent ribosomal RNA synthesis centers (when visible)

Protein Synthesis:

• Golgi Apparatus (#1,#2): Highly developed attacks of flattened sacs and nearby vesicles
  • Usually, more than one is distributed around the nucleus
  • Modifies, sorts, and packages proteins for delivery to specific locations
  • Critical for synaptic protein trafficking and membrane maintenance
• Endoplasmic Reticulum (ER):
  • Rough ER: Cisternae with bound ribosomes for protein synthesis
    • Nissl Substance: Distinctive neuronal feature consisting of clusters of RER and polyribosomes
  • Smooth ER: Ribosome-free cisternae involved in lipid synthesis and calcium regulation

Metabolic Systems:

• Mitochondria: Abundant organelles distributed throughout the soma and processes
  • Generate ATP for high-energy neuronal activities
  • Power ion movement during synaptic transmission
• Lysosomes: Membrane-bound organelles containing digestive enzymes
  • Break down cellular waste and damaged organelles
• Lipofuscin Granules: Contain incompletely digested cellular debris
  • Age-related accumulation
• Glycogen Granules: Large numbers to maintain high rates of metabolic activity

Cytoskeleton:

• Microtubules: Long, hollow tubules also involved in the transport of cellular components
• Neurofilaments: Intermediate filaments providing structural integrity
• Actin Filaments: Small dynamic filaments that maintain cell shape, dendritic spine formation and plasticity, and axonal growth during development

Dendrites

Pyramidal neurons possess elaborate dendritic trees that serve as the primary sites for synaptic input integration. These structures exhibit remarkable plasticity throughout life.

Dendritic Architecture:

• Apical Dendrite: Extends from the top of the soma towards the cortical surface
• Dendritic Spines: Small protrusions (1-2 μm) that dramatically increase synaptic surface area
  • Morphology: Mushroom-shaped spines
    • Occasional longitudinal sections (#1,#2) showing connection to a dendrite
    • Most profiles are cross-sections (#1,#2)
  • Dynamic Nature: Continuously remodels based on synaptic activity
  • Plasticity: Key substrates for learning and memory function

The surrounding neuropil contains the profiles of many dendrites from other neurons.

Dendritic Organelles:

• Golgi Outposts: Satellite Golgi apparatus are often found in larger dendrites
  • Enable local protein processing and trafficking
• Mitochondria: meet local energy demands and sustain electrical activity
• Endoplasmic Reticulum (ER):
  • Dendrites contain rough and smooth ER
  • Smooth ER within spines (#1,#2) is important in calcium regulation at synapses

Dendritic Cytoskeleton:

• Microtubules (#1,#2): Long, hollow tubules also involved in the transport of cellular components
  • Motor Proteins: Kinesin and dynein attach and crawl along microtubules
• Neurofilaments: Intermediate filaments providing structural integrity
• Actin Filaments: Important in dendritic spine formation and plasticity

Axons

While the pyramidal neuron's own axon may not be visible in every section, the neuropil contains numerous axons from other neurons, illustrating the complexity of cortical connectivity.

Axon Classification:

• Unmyelinated Axons (#1,#2): Smaller diameter fibers (0.1-1.0 µm)
  • Slower conduction velocities
  • Energy-efficient for short-distance communication
• Myelinated Axons (#1,#2): Larger-diameter fibers wrapped in myelin sheaths
  • Myelin Sheath: Insulating layers produced by oligodendrocytes
    • Oligodendrocytes often appear darker than other cells or processes
  • Faster Conduction: Saltatory propagation between nodes of Ranvier
  • Long-Distance Projections: Interconnect distant neurons

Axon Ultrastructure:

• Microtubules: Provide structural support and transport pathways
• Neurofilaments: Maintain axon diameter and mechanical strength
• Mitochondria: Meet energy demands along the axon length
• Smooth ER: Absence of rough ER distinguishes axons from dendrites

Synaptic Terminals and Neurotransmission

Pyramidal neurons integrate thousands of synaptic inputs across their dendritic trees. The axons of other neurons end in axon terminals (#1,#2) that form synapses (#1,#2), highly specialized structures optimized for rapid chemical signaling between neurons, with the dendritic spines.

Axon Terminal:

• Synaptic Vesicles: Small membrane-bound vesicles containing neurotransmitters
• Mitochondria: Provide ATP for vesicle recycling and calcium pumping
• Smooth ER: Regulates local calcium concentrations

Neurotransmission:

• Action Potential: Propagates along the axon, arriving at the axon terminal
• Calcium Influx: Depolarization opens voltage-gated Ca2+ channels
• Vesicle Fusion: Calcium triggers proteins to fuse vesicles with the plasma membrane (exocytosis)
• Neurotransmitter Release: Chemical signals cross the synaptic cleft
• Receptor Activation: Neurotransmitters bind to postsynaptic receptors to generate an electrical response

Astrocytes

Astrocytes are the largest and most abundant glial cell type, providing essential support for neuronal function.

Structure:

• Stellate Morphology: Star-shaped with numerous branching processes
• Process Organization: Irregular, angular-shaped terminal branches that fill empty spaces and ensheath synapses in the neuropil
• Nuclear Characteristics: Large, pale nucleus with dispersed chromatin (euchromatin)
• Glial Filaments: Larger processes contain bundles of intermediate filaments of glial fibrillary acidic protein (GFAP)

Functional Roles:

• Metabolic Support: Glucose metabolism and lactate provision to neurons
• Neurotransmitter Clearance: Uptake and recycling of glutamate and other transmitters
• Ion Homeostasis: Maintenance of extracellular potassium levels
• Synaptic Modulation: Active participation in synaptic transmission
• Blood-Brain Barrier: Formation and maintenance with endothelial cells