Neurophysiology

General Functions of the Nervous System

  • Nervous System: Communication and control system of the body.

    • Collects Information:

    • Receptors detect stimuli and send sensory signals to the spinal cord and brain.

    • Processes and Evaluates Information:

    • Brain and spinal cord determine the appropriate response to sensory input.

    • Initiates Response:

    • Brain and spinal cord send motor output via nerves to effectors (muscles or glands).

Organization of the Nervous System

  • Structural Organization:

    • CNS (Central Nervous System):

    • Composed of the brain and spinal cord.

    • PNS (Peripheral Nervous System):

    • Composed of nerves (fiber bundles) and ganglia (clusters of cell bodies along nerves).

  • Functional Organization:

    • Sensory versus Motor:

    • Sensory Nervous System (Afferent):

      • Receives sensory information from receptors and transmits it to the CNS.

      • Somatic Sensory System: Detects stimuli that we consciously perceive.

      • Example: Signals from eyes, ears, and skin.

      • Visceral Sensory System: Detects stimuli typically not consciously perceived.

      • Example: Signals from heart and kidneys.

    • Motor Nervous System (Efferent):

      • Initiates motor output and transmits it from CNS to effectors.

      • Somatic Motor System: Sends voluntary signals to skeletal muscles.

      • Autonomic Motor System (Visceral Motor): Sends involuntary commands to heart, smooth muscle, and glands.

      • Split into sympathetic and parasympathetic divisions.

Relationship of Neurons and Nerves

  • Nerve: Bundle of parallel axons in the PNS.

    • Nerves have protective connective tissue wrappings:

    • Epineurium: Thick layer of dense irregular connective tissue enclosing the entire nerve.

    • Perineurium: Dense irregular connective tissue wrapping around fascicles (small bundles of axons in a nerve).

    • Endoneurium: Delicate layer of areolar connective tissue wrapping around individual axons, separating and electrically insulating each axon.

  • Structural Classification of Nerves:

    • Cranial Nerves: Extend from the brain.

    • Spinal Nerves: Extend from the spinal cord.

  • Functional Classification of Nerves:

    • Sensory Nerves: Contain sensory neurons sending signals to the CNS.

    • Motor Nerves: Contain motor neurons sending signals from the CNS.

    • Mixed Nerves: Contain both sensory and motor neurons; most named nerves fall into this category.

    • Individual axons in mixed nerves transmit only one type of information.

General Characteristics of Neurons

  • Neurons (Nerve Cells): Have critical traits:

    • Excitability: Responsiveness to a stimulus causing a change in the cell's membrane potential.

    • Conductivity: Ability to propagate electrical signals, with voltage-gated channels opening sequentially.

    • Secretion: Release of neurotransmitter in response to conductive activity, allowing messages to influence target cells.

    • Extreme Longevity: Neurons can live for a person's lifetime.

    • Amitotic: After fetal development, most neurons lose the ability to undergo mitotic activity.

Neuron Structure

  • Parts of a Neuron:

    • Cell Body (Soma):

    • Plasma membrane enclosing cytoplasm (perikaryon).

    • Contains the nucleus, initiates graded potentials, receives signals from dendrites, conducts these potentials to the axon.

    • Contains chromatophilic substance (Nissl bodies) comprised of ribosomes (free and bound).

    • Dendrites:

    • Short, unmyelinated processes that branch off the cell body.

    • Function to receive input and transfer it to the cell body.

    • Axon:

    • Long process emanating from the cell body, makes contact with other neurons, muscular cells, or glands.

    • Attaches to cell body at axon hillock (triangular region of the soma).

    • Contains axoplasm (cytoplasm) and axolemma (membrane).

    • Splits into axon collaterals and ends in telodendria (axon terminals), with synaptic knobs at the tips.

  • Cytoskeleton:

    • Composed of microfilaments, intermediate filaments, and microtubules.

    • Intermediate filaments are termed neurofilaments and aggregate to form bundles known as neurofibrils, providing tensile strength to neurons.

Neuron Transport

  • Axonal Transport:

    • Axons transport material to and from the cell body.

    • Anterograde Transport: Moves newly synthesized material toward synaptic knobs.

    • Retrograde Transport: Moves used materials back to the cell body for breakdown and recycling.

    • Fast Axonal Transport: Occurs at about 400extmm/day400 ext{ mm/day}, involves movement along microtubules powered by motor proteins that split ATP. It can be both anterograde (toward synaptic knobs) and retrograde (back to cell body).

    • Slow Axonal Transport: Occurs at about 0.1extto3extmm/day0.1 ext{ to } 3 ext{ mm/day} resulting from the flow of axoplasm, moving substances only from the cell body toward the knob.

Classification of Neurons

  • Structural Classification:

    • Multipolar Neurons: Many dendrites, one axon (most common type).

    • Bipolar Neurons: One dendrite and one axon (limited number, e.g., retina of the eye).

    • Unipolar Neurons (Pseudounipolar): One axon extends from the soma, splits into two processes.

    • Peripheral process with several receptive dendrites and a central process leading to synaptic knobs in the CNS.

    • Anaxonic Neurons: Have dendrites but no axons; typically function as interneurons in the CNS.

  • Functional Classification:

    • Sensory Neurons (Afferent): Conduct input from somatic and visceral receptors to the CNS; primarily unipolar (some bipolar).

    • Motor Neurons (Efferent): Conduct output from the CNS to effectors; all are multipolar.

    • Interneurons (Association Neurons): Process and integrate information from multiple neurons, communicate between sensory and motor neurons; 99% of neurons in the CNS are typically multipolar.

Synapses

  • Synapse: Connection point between a neuron and another neuron or effector.

    • Types:

    • Chemical Synapses: Far more common; involve neurotransmitter release.

    • Electrical Synapses: Fast connections with no synaptic delay due to gap junctions between presynaptic and postsynaptic neurons.

  • Events of Chemical Synaptic Communication:

    • Presynaptic neuron's axon terminal produces signal, releasing neurotransmitter.

    • Neurotransmitter diffuses across the synaptic cleft and binds to postsynaptic receptors.

    • Binding initiates a postsynaptic potential (a graded potential).

    • There is a synaptic delay due to the time taken for these events to occur.

General Characteristics of Glial Cells

  • Glial Cells (Neuroglia): Nonexcitable support cells in the CNS and PNS, much smaller than neurons, but vastly outnumber them and contribute about half the volume of the nervous system.

    • Characteristics:

    • Capable of mitosis.

    • Protect and nourish neurons.

    • Provide structural scaffolding and guide migrating neurons during development.

    • Critical for normal function at neural synapses.

Types of Glial Cells in CNS

  • Astrocytes: Star-shaped, most abundant in CNS, help form the blood-brain barrier, regulate interstitial fluid composition, provide structural framework, assist with development, and replace dead neurons.

  • Ependymal Cells: Line the internal cavities of the brain and spinal cord, form the choroid plexus with blood capillaries, help produce cerebrospinal fluid (CSF), and have cilia to circulate CSF.

  • Microglia: Small, rare cells that act as phagocytes to remove debris and engulf infectious agents.

  • Oligodendrocytes: Large cells that wrap axons of neurons to form myelin sheath, allowing for faster action potential propagation.

Types of Glial Cells in PNS

  • Satellite Cells: Surround neuronal cell bodies in ganglia, insulating and regulating nutrient/waste exchange.

  • Neurolemmocytes (Schwann Cells): Encase PNS axons with myelin, permitting faster action potential propagation.

Myelination

  • Myelination: Process of wrapping an axon with myelin by glial cells (neurolemmocytes in PNS and oligodendrocytes in CNS).

    • Function: High lipid content provides insulation and allows for quick action potential propagation.

    • Forming Myelin Sheath: Involves several layers of membrane from glial cells surrounding the axon, creating neurilemma.

    • Neurofibril Nodes (Nodes of Ranvier): Gaps between myelinating neurolemmocytes.

Axon Regeneration

  • PNS Axon Regeneration: Possible if the neuron cell body remains intact and sufficient neurilemma is present. The success rate is higher if damage is minimal or distance from the site of injury to innervated structure is short.

  • Steps of Regeneration: 1) Axon severed by trauma.
    2a) Proximal to the cut: axon seals off and swells.
    2b) Distal to the cut: axon and sheath degenerate (Wallerian degeneration) but neurilemma survives.
    3) Neurilemma and endoneurium form a regeneration tube; axon regenerates guided by nerve growth factors.
    4) Axon reinnervates original target or sensory receptor.

  • CNS Axon Regeneration: Extremely limited.

    • Oligodendrocytes secrete growth-inhibiting molecules, and regrowth is obstructed by scars from astrocytes and connective tissue.

Classification of Channels and Pumps

  • Pumps: Membrane proteins that maintain concentration gradients by moving substances against their gradients, requiring cellular energy.

    • Examples: Sodium-potassium pumps, calcium pumps.

  • Channels: Protein pores that allow ions to move down their concentration gradients.

    • Types:

    • Leak Channels: Always open for diffusion.

    • Chemically Gated Channels: Closed until neurotransmitter binds.

    • Voltage-Gated Channels: Open when membrane charges change; sodium channels have three states.

    • Modality Gated Channels: Open in response to other stimuli.

Neurons and Ohm's Law

  • Neuron Activity: Dependent on electrical current, defined by voltage, current, and resistance.

    • Ohm's Law: Current = voltage/resistance; increased voltage or decreased resistance increases current.

Neurons at Rest

  • Characteristics: Ions unevenly distributed due to pumping actions, with potassium (K+K^+) being higher in the cytosol and sodium (Na+Na^+), chloride (Cl−Cl^-), and calcium (Ca2+Ca^{2+}) being higher in interstitial fluid.

  • Resting Membrane Potential (RMP): Typically −70extmV-70 ext{ mV}; measured via microelectrodes.

    • Main Ion Movement:

    • $K^+$ diffusion primarily establishes RMP, while $Na^+$ also influences it but to a lesser degree.

    • Role of Na+/K+ Pump: Maintains gradients by pushing 3 $Na^+$ out and 2 $K^+$ in, contributing approximately −3extmV-3 ext{ mV} to RMP.

Receptive Segment

  • Graded Potentials: Triggered by neurotransmitters binding to chemically gated ion channels.

    • Excitatory and Inhibitory Postsynaptic Potentials (EPSPs and IPSPs):

    • EPSPs: Depolarizations caused by cation entry, making the inside of the neuron more positive.

    • IPSPs: Hyperpolarizations caused by either cation exit or anion entry, making inside more negative.

Initial Segment

  • Summation of EPSPs and IPSPs: Occurs at the axon hillock; threshold for action potential generation is about −55extmV-55 ext{ mV}.

    • Types of Summation:

    • Spatial Summation: Multiple locations receive neurotransmitter simultaneously.

    • Temporal Summation: A single presynaptic neuron releases neurotransmitter multiple times in a quick succession.

Conductive Segment

  • Propagation of Action Potential: Involves depolarization and repolarization; all-or-none law applies.

    • Depolarization triggers voltage-gated Na+Na^+ channels, followed by repolarization via K+K^+ channels.

  • Refractory Period: Period post-action potential during which another cannot be immediately fired. It consists of:

    • Absolute Refractory Period: No stimulus can initiate another action potential.

    • Relative Refractory Period: A stronger-than-normal stimulus can initiate another action potential.

Transmissive Segment

  • Arrival of action potential triggers voltage-gated Ca2+Ca^{2+} channels, allowing calcium to enter and trigger neurotransmitter release through exocytosis into the synaptic cleft.

Graded vs. Action Potentials

  • Graded Potentials: Variable in magnitude, localized, and can be either positive or negative.

  • Action Potentials: Always the same size, propagate over long distances, and involve sequential changes in voltage across the membrane.

Velocity of Action Potential Propagation

  • Conduction Speed: Depends on axon thickness and myelination; thicker and myelinated axons conduct faster.

    • Nerve Fiber Groups:

    • Group A: Fast conduction (up to 150extm/s150 ext{ m/s}), myelinated, large diameter.

    • Group B and C: Conduct much slower (1 to 15 m/s), mostly small and unmyelinated.

Frequency of Action Potentials

  • Varies with stimulus strength; brighter lights cause more frequent action potentials in the optic nerve.

Classification of Neurotransmitters

  • Neurotransmitters: Small organic compounds released from neurons in response to action potentials.

  • Types of Neurotransmitters:

    • Acetylcholine: Used in peripheral nervous system for muscle stimulation.

    • Biogenic Amines: Include catecholamines (dopamine) and indolamines (serotonin).

    • Amino Acids: Include common transmitters like glutamate and GABA.

    • Neuropeptides: Chains of 2 to 40 amino acids, including substances like endorphins.

Features of Acetylcholine (ACh)

  • ACh clearance may occur via degradation, reuptake, or diffusion; its effect depends on receptor type.

    • Types of ACh Receptors:

    • Nicotinic Receptors: Directly cause excitatory potentials (EPSPs).

    • Muscarinic Receptors: Engage G proteins and produce various effects (EPSPs or IPSPs).