Neuronal Structure and Function

Introduction

• The nervous system has three main functions: sensory input, integration, and motor output. Sensory receptors detect changes in the internal and external environments and send action potentials to the brain and spinal cord for processing.
• The central nervous system (CNS) then generates motor commands that neurons deliver to muscles and glands to produce a response.
• Neurons communicate with target organs through two types of signaling: neural and endocrine.
  • Neural signaling involves action potentials traveling along a presynaptic neuron and transmitting to a postsynaptic cell via electrical or chemical synapses.
  • Endocrine signaling involves the synthesis and release of hormones into the bloodstream to reach target organs and acts more slowly than neural signaling.

Structure of a Neuron

• The cell body (soma) contains the cytoplasm, nucleus, and organelles needed for protein and ATP synthesis. Because mature neurons lack centrioles, they cannot undergo mitosis. Collections of neuronal cell bodies form gray matter; in the CNS, they are called nuclei, and in the peripheral nervous system (PNS), they are called ganglia.
• Dendrites are branched extensions of a neuron that receive synaptic signals from other neurons and carry those signals toward the cell body.
• The Axon is a long projection from the cell body, which conducts action potentials away from the cell body to other target neurons and tissues.
• The myelin sheath is a lipid-rich insulating layer formed by oligodendrocytes in the CNS and Schwann cells in the PNS. It increases the speed of action potential conduction and forms the white matter of the brain and spinal cord. Axons may be myelinated or unmyelinated.
• The axon hillock is the cone-shaped region where the axon begins; it serves as the trigger zone for initiating action potentials. It has the lowest action potential threshold in the cell because of its high density of voltage-gated Na⁺ channels.
• Nodes of Ranvier are gaps in the myelin sheath where ion channels are concentrated, enabling saltatory conduction.
• The axon terminal is the distal end of the axon where the neuron communicates with another cell at the synapse.

Neuron Morphologies

• Multipolar neurons have one axon and multiple dendrites that project directly into the cell body; they are the most common neuronal type in the CNS and include most motor neurons.
• Bipolar: Neurons with one axon and one dendrite; found in sensory structures like the retina and olfactory epithelium.
• Unipolar: Neurons with a single process extending from the cell body. These are uncommon in humans but are found in the cochlea.
• Pseudounipolar: Sensory neurons with one process that splits into peripheral and central branches; common in dorsal root ganglia.
• Anaxonic: Neurons with no obvious axon; involved in local signaling within the CNS.
• Pyramidal cells: Large multipolar neurons with a pyramid-shaped soma that can integrate multiple afferent signals. Most common in the cerebral cortex and hippocampus.

CNS

The CNS consists of the brain and spinal cord.

• Brain – Integrates sensory input, generates motor output, and supports higher functions such as thinking and learning.
• Spinal Cord – Contains long sensory and motor pathways that carry information between the body and the CNS. Interneurons provide local connections within the cord.

The primary functions of the CNS include:

• Integration and processing of input from the PNS to generate an appropriate response.
• Generates motor and involuntary motor output by sending signals to muscles and glands.
• The brain supports cognition, memory, emotion, language, problem-solving, and executive control.
• Regulates homeostasis through autonomic and endocrine interactions, maintaining respiration, CV activity, thermoregulation, and fluid balance
• The spinal cord mediates rapid, involuntary reflexes.

PNS

The PNS includes all neural structures outside the CNS.

• Sensory (afferent) neurons: Carry information from the external environment and internal organs to the CNS.
• Motor (efferent) neurons: Somatic motor neurons send action potentials from the CNS to skeletal muscle.
• Enteric neurons: Form an independent neural network around the GI tract, modulated by autonomic input.
• Autonomic neurons: Control involuntary functions via the sympathetic and parasympathetic divisions.

Peripheral Nerve Anatomy

• Schwann Cells produce myelin around axons in the PNS.
• Endoneurium is a thin connective tissue layer that surrounds individual axons.
• Perineurium encases groups of nerve fibers, forming nerve fascicles.
• Epineurium is a thick outer connective tissue layer that encloses multiple fascicles and associated blood vessels in a peripheral nerve.

Peripheral Nerve Fiber Classification

• Peripheral nerve fibers are categorized by diameter, degree of myelination, and conduction velocity, enabling systematic classification of sensory and motor fibers into functional groups.
• These classifications (A, B, and C fibers) help predict how different fibers respond to injury, disease, and anesthetic interventions.

Action Potential Propagation

• An action potential propagates in one direction along the axon through the formation of local circuits. At rest, the intracellular surface of the membrane is negatively charged relative to the outside.
• When an action potential occurs, the affected segment of the membrane becomes positively charged inside, but the depolarization is limited to that segment. Ions move within this active segment, generating a local current that spreads to the neighboring portion of the membrane.
• The neighboring segment depolarizes in response to this current. If the depolarization reaches threshold potential, a new action potential is triggered.
• The local current decays exponentially along the axon, but propagation continues if the threshold is reached in successive segments.
• This sequential chain of local depolarizations continues until the action potential reaches its final target, such as a synapse or effector cell.¹

Factors affecting the speed of action potential conduction include:

• Axon Diameter: Larger-diameter axons conduct action potentials faster because they offer less internal resistance to the flow of ions.
• Transmembrane Resistance: Higher resistance across the membrane reduces leakage of ions, allowing depolarizing currents to travel farther and faster along the axon.
• Membrane Capacitance: Lower membrane capacitance allows the membrane potential to change more quickly in response to ionic currents, increasing conduction speed.
• Temperature: Higher temperatures generally increase conduction speed by accelerating the kinetics of ion channel opening and closing, while lower temperatures slow conduction.
• Myelination:
  • Insulation: a lipid-rich sheath surrounds the axon and acts as an insulating layer, preventing leakage of current across the membrane.
  • Increases conduction speed by reducing membrane capacitance and increasing transmembrane resistance, allowing depolarizing currents to travel along the axon without losing strength. Unmyelinated nerve conduction 2 m/s vs myelinated nerve conduction up to 120 m/s
  • Saltatory conduction: Myelinated axons have nodes of Ranvier, gaps where voltage-gated Na⁺ channels are concentrated. Allowing action potential to jump from node to node, instead of propagating continuously along the membrane.
  • Energy efficiency: Restricting ion flux to the nodes of Ranvier, which reduces the metabolic energy required to restore ion gradients via Na/K⁺ ATPase pumps.
  • Axon protection and support: Myelin provides structural support to axons and protects them from mechanical and chemical damage.

Clinical Implications

Local Anesthetics

• Local anesthetics (e.g., lidocaine, bupivacaine) block voltage-gated Na⁺ channels, preventing depolarization and the propagation of action potentials along sensory and motor axons. These agents preferentially block actively firing neurons, such as nociceptive fibers, by binding to open or inactivated channels in a state-dependent manner. This mechanism allows for targeted analgesia during regional or local anesthesia while sparing less active motor fibers at lower concentrations.⁶
• Sensitivity to local anesthetics varies by fiber type:
  • Small-diameter fibers are more sensitive than large-diameter fibers.
  • Myelinated fibers are generally more sensitive than unmyelinated fibers, likely due to the dense clustering of Na⁺ channels at nodes of Ranvier.
  • Consequently, intermediate-sized myelinated fibers (nociceptive and autonomic) are most susceptible to blockade. In contrast, fibers mediating touch, pressure, and proprioception are less sensitive, and unmyelinated C fibers are the most resistant.⁶

NMBAs

• NMBAs act at the neuromuscular junction, where the presynaptic terminal of a motor neuron releases acetylcholine (ACh) onto postsynaptic nicotinic receptors on skeletal muscle fibers. Under normal physiology, ACh binding triggers depolarization of the muscle end plate, leading to muscle contraction.
• Depolarizing NMBAs (e.g., succinylcholine) function as ACh receptor agonists, causing prolonged depolarization at the motor end plate. This depolarized state prevents resetting of voltage-gated Na⁺ channels, resulting in a refractory period during which additional action potentials cannot be generated. The result is transient but rapid-onset paralysis, which is clinically useful for procedures such as intubation.⁷
  Nondepolarizing NMBAs (e.g., rocuronium) function as competitive antagonists at nicotinic receptors. By blocking Ach from binding, they prevent end-plate depolarization and inhibit neuromuscular signal transmission. This leads to controlled skeletal muscle paralysis, frequently used to optimize surgical conditions and facilitate mechanical ventilation.⁷

Demyelination

• The myelin sheath is essential for the rapid conduction of action potentials along motor and sensory axons. Autoimmune diseases that destroy myelin include:
  • Multiple Sclerosis – affects the CNS (Link)
  • Guillain-Barré Syndrome – affects the PNS (Link)
• Demyelination disrupts action potential propagation: although clusters of Na⁺ channels remain, exposed areas of the axon lack sufficient channels, preventing effective conduction. This results in deficits in sensation, motor function, autonomic function, or cognition, depending on the location and extent of demyelination.¹