2.1 Structure and function of neurons and glial cells

Neurons and glial cells are the building blocks of our nervous system. Neurons transmit electrical signals, while glial cells provide support and protection. Together, they form the complex network that allows us to think, feel, and move.

Understanding these cells is crucial for developing neuroprosthetics. By mimicking or interfacing with neurons and glia, we can create devices that restore lost function or enhance existing capabilities in the nervous system.

Neuron and Glial Cell Structure and Function

Components and functions of neurons

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• Soma (cell body)
  • Houses the nucleus and organelles essential for cellular functions (protein synthesis, energy production)
  • Integrates incoming signals from dendrites to generate action potentials
• Dendrites
  • Highly branched extensions that receive and process signals from other neurons
  • Covered in dendritic spines, small protrusions that form synapses with axon terminals
  • Increased surface area enhances the neuron's ability to receive and integrate multiple signals
• Axon
  • Elongated, cable-like extension that conducts electrical signals away from the soma
  • Insulated by a myelin sheath formed by oligodendrocytes (CNS) or Schwann cells (PNS)
  • Myelin sheath enables faster signal propagation through saltatory conduction (nodes of Ranvier)
• Axon terminal
  • Specialized structure at the end of the axon that releases neurotransmitters into the synaptic cleft
  • Contains synaptic vesicles filled with neurotransmitters (glutamate, GABA, dopamine)
  • Forms synapses with dendrites or cell bodies of target neurons, or with muscle fibers or glands
• Synapses
  • Junctions between the axon terminal of one neuron and the dendrite, soma, or axon of another neuron
  • Can be chemical synapses (neurotransmitter release) or electrical synapses (gap junctions)
  • Site of information transfer and processing in neural circuits

Types and roles of glial cells

• Astrocytes
  • Star-shaped cells that provide structural and metabolic support to neurons
  • Maintain the blood-brain barrier by forming tight junctions with endothelial cells
  • Regulate neurotransmitter levels (glutamate uptake) and ion concentrations (K+ buffering) in the synaptic cleft
  • Release gliotransmitters (ATP, D-serine) to modulate synaptic transmission and plasticity
• Oligodendrocytes (CNS) and Schwann cells (PNS)
  • Form the myelin sheath around axons, providing electrical insulation and increasing conduction velocity
  • Oligodendrocytes can myelinate multiple axons, while Schwann cells myelinate a single axon segment
  • Support axonal integrity and survival through trophic factor release (BDNF, NGF)
• Microglia
  • Resident immune cells of the CNS that constantly survey the brain for damage or infection
  • Phagocytose cellular debris, apoptotic cells, and foreign pathogens to maintain brain homeostasis
  • Secrete pro-inflammatory (TNF-α, IL-1β) and anti-inflammatory (IL-10, TGF-β) cytokines to regulate neuroinflammation
  • Contribute to synaptic pruning during development and in response to injury or disease
• Ependymal cells
  • Cuboidal or columnar epithelial cells that line the ventricles and central canal of the spinal cord
  • Possess cilia that facilitate the circulation of cerebrospinal fluid (CSF) throughout the ventricular system
  • Form a barrier between the CSF and brain parenchyma, regulating the exchange of molecules
  • Contain neural stem cells in specific regions (subventricular zone) that give rise to new neurons and glia

Process and significance of neurogenesis

• Neurogenesis involves the proliferation, migration, and differentiation of neural stem cells into mature neurons
• Primarily occurs during embryonic and early postnatal development, establishing the basic structure of the nervous system
• In adults, neurogenesis is largely restricted to the subgranular zone of the hippocampal dentate gyrus and the subventricular zone of the lateral ventricles
• Hippocampal neurogenesis is associated with learning, memory formation, and mood regulation (depression, anxiety)
• Subventricular zone neurogenesis generates interneurons that migrate to the olfactory bulb, contributing to olfactory learning and discrimination
• Enhancing neurogenesis through exercise, environmental enrichment, or pharmacological interventions may promote brain repair and recovery after injury (stroke, traumatic brain injury) or in neurodegenerative diseases (Alzheimer's, Parkinson's)

Mechanisms of neuronal communication

1. Electrical signaling within neurons
   • Neurons maintain a resting membrane potential of -60 to -70 mV through the action of ion pumps (Na+/K+ ATPase) and selective ion channels
   • Action potentials are generated when the membrane potential reaches a threshold (-55 mV) due to sufficient depolarization
     • Depolarization: Voltage-gated Na+ channels open, allowing Na+ influx and rapid rise in membrane potential
     • Repolarization: Voltage-gated K+ channels open, allowing K+ efflux and return to resting membrane potential
     • Refractory period: Na+ channels are inactivated, and the neuron cannot generate another action potential until they recover
   • Action potentials propagate along the axon in an all-or-none manner, maintaining their amplitude
2. Chemical signaling between neurons (synaptic transmission)
   • Action potentials arriving at the axon terminal trigger the opening of voltage-gated Ca2+ channels
   • Ca2+ influx causes synaptic vesicles to fuse with the presynaptic membrane and release neurotransmitters into the synaptic cleft
   • Neurotransmitters diffuse across the cleft and bind to receptors on the postsynaptic cell
     • Ionotropic receptors (ligand-gated ion channels) mediate fast synaptic transmission by directly opening ion channels (AMPA, NMDA, GABAA receptors)
     • Metabotropic receptors (G protein-coupled receptors) mediate slower, modulatory effects by activating intracellular signaling cascades (mGluRs, 5-HT receptors)
   • Excitatory neurotransmitters (glutamate) depolarize the postsynaptic cell, while inhibitory neurotransmitters (GABA, glycine) hyperpolarize it
   • Neurotransmitters are cleared from the synaptic cleft by reuptake into the presynaptic terminal or surrounding glial cells, or by enzymatic degradation (acetylcholinesterase)
   • Synaptic plasticity, the strengthening or weakening of synapses in response to activity, underlies learning and memory ($LTP$, $LTD$)