Vander's Chapter 6

6.1 Structure and Maintenance of Neurons

• The nervous system is divided into:

  • The central nervous system (CNS): brain and spinal cord.

  • The peripheral nervous system (PNS): nerves connecting the brain and spinal cord to the body.

• A neuron is the functional unit, generating electrical signals to communicate within itself or with neighbors.

• Electrical signals trigger neurotransmitter release to communicate with other cells.

• Most neurons integrate inputs from many other neurons.

• Glial cells are non-neuronal cells that support neurons, but don't directly participate in electrical communication.

Neuron Structure

• Neurons come in various sizes/shapes, but share features for cell-to-cell communication via long extensions (processes).

  • Cell Body (soma):

    • Contains the nucleus, ribosomes, and machinery for protein synthesis.

  • Dendrites:

    • Branched outgrowths that receive incoming information from other neurons.

    • Dendritic spines increase surface area for signal reception, especially in the CNS (up to 400,000).

  • Axon:

    • Extends from the cell body and carries outgoing signals to target cells; varies in length from microns to over a meter.

    • Axon Hillock (initial segment):

      • Where electrical signals are generated in most neurons.

    • Collaterals: Branches of the axon.

    • Axon Terminal:

      • Releases neurotransmitters.

    • Varicosities: Bulging areas along the axon that release chemical messengers.

    • The greater the degree of branching, the greater the cell's sphere of influence.

Myelin Sheath

• Covers the axons of many neurons (20-200 layers of modified plasma membrane).

  • Oligodendrocytes (CNS):

    • Glial cells that form myelin on up to 40 axons.

  • Schwann Cells (PNS):

    • Form individual myelin sheaths surrounding 1-1.5 mm long segments.

  • Nodes of Ranvier:

    • Spaces between myelin sections where axon plasma membrane is exposed to extracellular fluid.

• Myelin speeds electrical signal conduction and conserves energy.

Axonal Transport

• Organelles/materials must move long distances (up to 1 meter) between the cell body and axon terminals.

• Axonal transport depends on:

  • Microtubules: Scaffolding "rails" running the axon's length.

  • Motor Proteins: Kinesins and dyneins.

• Kinesin:

  • Anterograde transport (cell body to axon terminals).

  • Moves nutrient molecules, enzymes, mitochondria, and neurotransmitter-filled vesicles.

  • Uses energy from ATP hydrolysis to "walk" along microtubules.

• Dynein:

  • Retrograde transport (axon terminals to cell body).

  • Carries recycled membrane vesicles, growth factors, and chemical signals.

  • Also the route for harmful agents to invade the CNS, including tetanus toxin, herpes simplex, rabies, and polio viruses.

6.2 Functional Classes of Neurons

• Nervous System:

  • CNS (brain and spinal cord).

  • PNS (neurons outside the CNS).

• Neuron: Basic cellular unit of the nervous system.

• Cell Body and Dendrites:

  • Receive information from other neurons (including dendritic spines).

• Axon:

  • Begins at axon hillock, ends at axon terminals; transmits information to other neurons or effector cells.

• Glia Cells:

  • Non-neuronal cells that do not directly participate in signaling but play supporting roles for neurons.

• Myelin:

  • Insulating sheath formed over certain neurons in CNS and PNS speeds transmission of signals; made of membranes of Schwann cells (PNS) or oligodendrocytes (CNS) that are interrupted periodically at nodes of Ranvier

• Neurotransmitters:

  • Chemical mediators released by neurons that act as signals between neurons or between neurons and other cells (e.g., muscle cells).

Neuron Classes (Figure 6.4a)

• Afferent Neurons:

  • Convey information from tissues and organs toward the CNS.

  • Have sensory receptors responding to physical or chemical changes.

  • Shape is distinct; single process associated with the cell body, which divides.

    • Peripheral and central processes.

  • Both the cell body and the long axon are outside the CNS; only part of the central process enters the brain or spinal cord.

• Efferent Neurons:

  • Convey information away from the CNS to effector cells like muscle, gland, or other cell types.

  • Shape like that shown in Figure 6.1.

  • Cell bodies and dendrites are within the CNS, and the axons extend to the periphery.

• Interneurons:

  • Connect neurons within the CNS.

  • Over 99% of all neurons are interneurons.

Nerves

• Groups of afferent and efferent neuron axons, myelin, connective tissue, and blood vessels in the PNS.

Interneurons

• Lie entirely within the CNS.

• Account for >99% of all neurons, with a wide range of properties and functions.

• Varying numbers are interposed between afferent and efferent neurons depending on the complexity of the action.

  • Knee-jerk reflex example of interaction without interneurons.

• Evoking memories of someone example for involving millions of interneurons.

Synapse

• Specialized junction between two neurons where one neuron alters the electrical and chemical activity of another.

• Signals transmitted via neurotransmitters that bind with specific protein receptors on the receiving neuron.

• Most synapses occur between an axon terminal and a dendrite/cell body.

• Presynaptic neuron conducts a signal toward a synapse.

• Postsynaptic neuron conducts signals away from a synapse.

• A single neuron can be postsynaptic to one cell and presynaptic to another (multineuronal pathway).

• Postsynaptic neurons can have thousands of synaptic junctions, allowing integration of signals from many presynaptic neurons.

• Information flow is an essential feature of homeostasis and allows for complex integration of physiological processes.

6.3 Glial Cells

• Account for fewer than half the cells in the human CNS.

• Surround the axon and dendrites of neurons and provide them with physical and metabolic support.

• Retain the capacity to divide throughout life, unlike most neurons.

• CNS tumors often originate from glial cells rather than from neurons.

Types of Glial Cells in the CNS (Figure 6.6)

• Oligodendrocytes:

  • Form the myelin sheath of CNS axons.

• Astrocytes:

  • Regulate the composition of the extracellular fluid in the CNS by removing potassium ions and neurotransmitters around synapses.

  • Stimulate the formation of tight junctions between the cells that make up the walls of capillaries found in the CNS, forming the blood-brain barrier.

  • Sustain neurons metabolically by providing glucose and removing ammonia.

  • Guide CNS neurons in embryos as they migrate to their destination, and stimulate neuronal growth by secreting growth factors.

  • Have ion channels, receptors for neurotransmitters, and the capability of generating weak electrical responses.

• Microglia:

  • Specialized, macrophage-like cells that perform immune functions in the CNS and contribute to synapse remodeling.

• Ependymal cells:

  • Line the fluid-filled cavities within the brain and spinal cord and regulate the production and flow of cerebrospinal fluid.

Glial Cells in the PNS

• Schwann cells:

  • Produce the myelin sheath of axons of peripheral neurons.

Glial Cells Summary

• Help regulate extracellular fluid composition

• Sustain neurons metabolically

• Form myelin

• Form the blood-brain barrier (selective filter for materials entering the CNS)

• Serve as guides for developing neurons

• Provide immune functions

• Regulate production of cerebrospinal fluid

6.4 Neural Growth and Regeneration

• Development begins with division of undifferentiated precursor cells (stem cells) that can develop into neurons or glia.

• Neuronal daughter cells differentiate, migrate to their final location, and send out processes.

• A specialized enlargement, the growth cone, forms the tip of each extending axon and finds the correct route/target. *As the axon grows, it is guided by:

  • Cell Adhesion Molecules on glia and embryonic neurons.

  • Soluble neurotrophic factors (growth factors) in extracellular fluid.

• Once the target is reached, synapses form.

• Alcohol, drugs, radiation, malnutrition, and viruses during pregnancy/infancy can cause permanent damage to the nervous system (e.g., microcephaly from Zika virus).

Apoptosis and Plasticity

• Many newly formed neurons and synapses degenerate (apoptosis).

  • As many as 50% to 70% of neurons programmed self-destruction.

  • Thought to refine/fine-tune connectivity. Likely reason humans don't retain pre-4-year-old memories.

• Plasticity: Brain's ability to modify its structure/function in response to stimulation/injury.

  • May involve generating new neurons, but mainly remodeling synaptic connections.

  • Stimulated by exercise and cognitively challenging activities.

• Critical time window for development exists for many neural systems at a young age.

  • Visual pathways: processing impaired if no visual stimulation is received during 1-2 years of age.
    Learning a language changes in plasticity:

  • Humans learn relatively quickly until adolescence, but learning becomes slower and more difficult from adolescence through adulthood.

• The basic shapes and locations of major neuronal circuits in the mature CNS do not change once formed.

• The creation and removal of synaptic contacts begun during fetal development continue throughout life as part of normal growth, learning, and aging.

• Ability to produce new neurons is retained in some brain regions throughout life.
  Stimulation and exercise increase neuron numbers in learning-associated brain regions.

• Effectiveness of some antidepressant medications has been shown to depend upon the production of new neurons in regions involved in emotion and motivation.

Regeneration of Axons

• Can repair themselves and restore significant function if damage occurs outside the CNS and doesn't affect the cell body.

  • The axon segment separated from the cell body degenerates.

  • The part of the axon still attached to the cell body creates a growth cone, which grows to the effector organ.
    *Return of function is delayed (1 mm per day).

• Spinal injuries typically crush rather than cut tissue, causing self-destruction (apoptosis) of oligodendrocytes.

  • Axons lose myelin sheath and cannot transmit effectively.

• Severed axons within CNS may grow small new extensions, but no significant regeneration occurs across the damaged site, with few well-documented reports of function return.

• Functional regeneration is prevented by:

  • Basic CNS neuron differences.

  • Inhibitory factors associated with glia.
    *Selection pressure during evolution likely limited growth in the mature CNS to minimize disruption of neuronal networks.

• Researchers are exploring ways to provide an environment to support axonal regeneration:

  • Creating tubes to support regrowth of severed axons

  • Redirecting axons to regions that lack growth-inhibiting factors

  • Preventing apoptosis of oligodendrocytes so myelin can be maintained

  • Supplying neurotrophic factors

• Researchers are also attempting to restore function by implanting undifferentiated stem cells that will develop into new neurons and replace missing neurotransmitters or neurotrophic factors.

  • Recently, promising techniques have been developed using stem cells isolated from adults, and using adult cells that have been induced to revert to a stem-cell-like state

6.5 Basic Principles of Electricity

• Physiological processes follow laws of chemistry and physics that determine charged molecule flux.

• Extracellular fluid: Predominant solutes ${Na}^+$ and ${Cl}^-$.

• Intracellular fluid: High concentrations of ${K}^+$ and ionized nonpenetrating molecules.

• Electrical phenomena occur at the plasma membrane and function in signal integration and communication.

• Like charges repel each other, opposite charges attract each other.

• Separated electrical charges of opposite sign have the potential to do work if they are allowed to come together.

• This potential is called an electrical potential or, because it is determined by the difference in the amount of charge between two points, a potential difference (often referred to simply as the potential). Volts are the units of electrical potential.

• The potential differences are small and are measured in millivolts $(1 mV = 0.001 V)$.

• Movement of electrical charge is called a current.

• The electrical potential between charges tends to make them flow, producing a current. If the charges are opposite, the current brings them toward each other; if the charges are alike, the current increases the separation between them.

• The amount of charge that moves—in other words, the magnitude of the current—depends on the potential difference between the charges and on the nature of the material or structure through which they are moving.

• The hindrance to electrical charge movement is known as resistance.

• If resistance is high, the current flow will be low.

  • Ohm's Law: $I = \frac{V}{R}$, Where:

    • $I= Current$

    • $V = Voltage$

    • $R = Resistance$

• Insulators: Materials with high electrical resistance reduce current flow.

• Conductors: Materials with low resistance allow rapid current flow.

• Water containing ions is a relatively good conductor of electricity.

• Intracellular and extracellular fluids contain many ions and can carry current.

• Lipids contain very few charged groups and cannot carry current.

• Lipid layers of the plasma membrane are regions of high electrical resistance separating intracellular/extracellular fluids.

6.6 The Resting Membrane Potential

• At rest, neurons have a potential difference across their plasma membranes, with the inside of the cell negatively charged with respect to the outside.

• The resting membrane potential is abbreviated $V_m$.

• Extracellular fluid is designated as the voltage reference point.
  *The magnitude of the resting membrane potential in neurons is generally in the range of $-40$ to $-90 mV$.

• The resting membrane potential holds steady unless changes in electrical current alter the potential.

• It exists because of tiny excesses of negative ions inside the cell and positive ions outside it. Electrical Interactions:

  • The excess negative charges inside are electrically attracted to the excess positive charges outside the cell, and vice versa.
    Tiny Excess Charges:

• The number of positive and negative charges that have to be separated across a membrane to account for the potential is actually an infinitesimal fraction of the total number of charges in the two compartments

Distribution of Ions

• $Na^+, K^+, Cl^−$ are present in the highest concentrations, and the membrane permeability to each is independently determined.

• The $Na^+ and K^+$ generally make the most important contributions in generating the resting membrane potential, but in some cells, $Cl^−$ is also a factor.
  Concentration differences for$Na^+$ and $K^+$ are established by the action of the sodium/potassium-ATPase pump (