Neurophysiology: Physical and Electrical Properties of the Nervous System

Classification of Neurons

Neurons are categorized by their structural morphology:

• Unipolar cells: Found in the autonomic nervous system.
• Bipolar cells: Specialized sensory neurons, such as those found in the retina.
• Pseudo-unipolar cells: The most common sensory neurons, which convey information from the PNS to the CNS (e.g., dorsal root ganglion cells).
• Multipolar cells: The most common type, designed to accommodate large amounts of synaptic input. This group includes motor neurons, pyramidal cells, and Purkinje cells.

Additionally, neurons can be classified by their functional role: sensory neurons (afferent), motor neurons (efferent), and interneurons.

Glial Cells: The Support Network

Glial cells are not merely "glue"; they are a critical support network that also participates in transmitting information. They are categorized into macroglia (large) and microglia (small).

1. Myelinating Glia: These cells provide insulation to increase conduction velocity.
   • Oligodendrocytes: Found in the CNS; one cell can myelinate parts of several different axons.
   • Schwann Cells: Found in the PNS; they may wrap around a single axon or several axons and provide trophic factors for repair.
2. Astrocytes: Star-shaped macroglia in the CNS that act as "scavengers". They regulate the environment by taking up excess $K^+$ ions, removing neurotransmitters from the synaptic cleft, and cleaning up extracellular debris.
3. Microglial Cells: The "defenders" of the nervous system. They function as phagocytes, constantly sampling the environment to clean up debris from dying cells or indicators of damage.

Clinical Note: Neuroinflammation Neuroinflammation is the CNS's response to injury or infection. While beneficial in the short term (e.g., microglia cleaning up debris), chronic or abnormal glial activity is linked to diseases like Alzheimer's, Parkinson's, and Multiple Sclerosis.

Electrical Properties and Membrane Potentials

The ability of a neuron to communicate depends on its plasma membrane, which separates the intracellular environment from the extracellular space. This separation creates electrical and concentration gradients.

The Electrochemical Gradient

At rest, ions are distributed unequally. For example, $Na^+$, $Cl^-$, and $Ca^{2+}$ concentrations are higher outside the cell, while $K^+$ is higher inside. Because the interior of the neuron is negatively charged, cations like $Na^+$ and $Ca^{2+}$ are electrically attracted to the inside. The electrochemical gradient is the combined influence of these concentration and electrical forces, determining the direction an ion will move.

Resting Membrane Potential

The resting membrane potential is the steady-state electrical charge across the membrane when no information is being transmitted. In most neurons, this is approximately $-60\text{ mV}$ to $-70\text{ mV}$. This negative state is maintained by three primary mechanisms:

1. **Leaky $K^+$channels**:$K^+$ moves out of the cell via passive diffusion.
2. $Na^+/K^+$ pump: This active transport mechanism uses ATP to move three $Na^+$ ions out of the cell for every two $K^+$ ions moved in.
3. Trapped Anions: Large, negatively charged molecules (like proteins) remain inside the cell because they are too large to pass through channels.

Membrane Channels

Four types of channels facilitate the movement of ions across the membrane:

• Leak channels: Always open; maintain the resting potential.
• Voltage-gated channels: Open in response to changes in electrical potential.
• Ligand-gated channels: Open when a specific neurotransmitter binds to them.
• Modality-gated channels: Respond to specific types of stimuli (e.g., mechanical or thermal).

Signal Propagation: Local and Action Potentials

Information travels through neurons via rapid changes in electrical potential.

Local Potentials

Local potentials are small, graded changes in membrane potential that spread only short distances. They can be either depolarizing (making the membrane less negative/excitatory) or hyperpolarizing (making the membrane more negative/inhibitory).

• Receptor Potentials: Generated at the peripheral receptors of sensory neurons (e.g., when a muscle is stretched).
• Synaptic Potentials: Generated at the postsynaptic membrane when neurotransmitters bind to receptors.

Local potentials can be integrated through temporal summation (rapid successive signals) or spatial summation (signals from different locations).

Action Potentials

When a local potential is strong enough to reach a specific threshold (typically $-55\text{ mV}$), an action potential is triggered. Unlike local potentials, action potentials are "all-or-none"—they occur at a constant magnitude regardless of stimulus strength.

The process follows a specific sequence:

1. Depolarization: Voltage-gated $Na^+$ channels open, and $Na^+$ rushes into the cell, making the interior positive.
2. Repolarization: $Na^+$ channels close, and voltage-gated $K^+$ channels open, allowing $K^+$ to exit the cell.
3. Hyperpolarization: $K^+$ channels remain open slightly too long, making the membrane even more negative than the resting state.

Exam Tip: Refractory Periods After an action potential, the neuron enters a refractory period. During the absolute refractory period, the membrane is completely unresponsive to new stimuli. During the relative refractory period, a much stronger stimulus is required to trigger another signal.

Improving Conduction Velocity

To move information quickly over long distances, the nervous system uses two adaptations:

1. Increased Axon Diameter: Larger axons allow for faster signal progression.
2. Myelination and Saltatory Conduction: Myelin acts as insulation. Instead of a continuous wave of depolarization, the signal "jumps" from one Node of Ranvier (unmyelinated gaps) to the next. This process is called saltatory conduction.

Neural Development and Clinical Applications

Neural stem cells are undifferentiated precursors that can self-renew and differentiate into both neurons and glial cells. They play a vital role in development and potentially in neural recovery after injury.

Demyelinating Diseases

When the myelin sheath is destroyed, signal conduction is disrupted, leading to sensory and motor deficits.

• Guillain-Barré Syndrome: An autoimmune attack on the myelin in the PNS. It often presents as ascending paralysis (starting from the feet) following an infection.
• Multiple Sclerosis (MS): An autoimmune attack on the oligodendrocytes in the CNS, resulting in plaques in the white matter. This can cause weakness, vision impairment, and coordination issues.