Chapter 12: Nervous Tissue



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Chapter 12: Nervous Tissue


Chapter Outline and Objectives

OVERVIEW OF THE NERVOUS SYSTEM

  1. Identify the structures that make up the nervous system.

  2. Classify the organs of the nervous system into central and peripheral divisions and their subdivisions.

  3. List and explain the three basic functions of the nervous system and indicate the direction of afferent and efferent information flow.

HISTOLOGY OF NERVOUS TISSUE

  1. List the three parts of a neuron.

  2. Describe the structures located in a neuron cell body and their functions.

  3. List the names given to collections of cell bodies in the CNS and PNS.

  4. Describe the function of the dendrites.

  5. Describe the direction of information flow through an axon.

  6. List the names given to collections of axons in the CNS and PNS and how they are bundled together.

  7. Identify neurons on the basis of their structural and functional classifications.

  8. Contrast the general functions of neuroglia and neurons.

  9. Describe the relative number of neuroglia compared to neurons.

  10. List the four types of neuroglia in the CNS and describe the function for each.

  11. List the two types of neuroglia in the PNS and describe the function for each.

  12. Identify the cells that produce myelin, describe how the sheath is formed, and discuss its function.

  13. Define the neurolemma and discuss its function.

  14. Describe the Nodes of Ranvier and tell why they are important for axon signal transmission.

  15. Discuss multiple sclerosis in terms of anatomical changes and causes.

  16. Describe the difference between gray and white matter, and give examples of each.

ELECTRICAL SIGNALS IN NEURONS

  1. Distinguish between action potential and graded potentials.

  2. Identify the basic types of ion channels and the stimuli that operate gated ion channels.

  3. Describe the ions, channels, and integral-protein pumps that contribute to generation of a resting membrane potential.

  4. Discuss the All or none principal in regards to neurons.

  5. Discuss the features of the graded potential including areas where generated, size, properties, and type.

  6. Describe the effect the sum of the excitatory and inhibitory stimuli has on the neuron.

  7. List the sequence of events involved in generation of a nerve impulse.

  8. Define and give a value for the threshold voltage.

  9. Describe the events involved in depolarization of the nerve cell membrane and tell which charges are located where.

  10. Describe the repolarization of the nerve cell membrane and tell which charges are located where.

  11. Define refractory period and describe why it occurs.

  12. Discuss how the sodium ion flow in one area of an axon leads to initiation of an action potential in an adjacent region of the axon membrane.

  13. Compare and contrast continuous and saltatory conduction.

  14. Outline the factors that alter the rate of action potential propagation along an axon.

SIGNAL TRANSMISSION AT SYNAPSES

  1. Describe the structure of a chemical synapse.

  2. Go through the sequence of events that allow an action potential on an axon to be transmitted into a graded potential on a postsynaptic membrane.

  3. Indicate the voltage changes associated with EPSPs and IPSPs, and how these potentials are related to various ion channels.

  4. Distinguish between spatial and temporal summation.

  5. Note that there must be a mechanism to diminish neurotransmitter concentrations in the synaptic cleft to be able to turn the stimulus off.

NEUROTRANSMITTERS

  1. Describe and give examples and functions of the various neurotransmitter classes.

  2. Be able to identify the group to which a specific neurotransmitter belongs.

  3. Describe the effect of various drugs and disorders on normal neurotransmitter function.

CIRCUITS IN THE NERVOUS SYSTEM

  1. Describe the various types of neuronal circuits in the nervous system.

Chapter Lecture Notes

Homeostasis

The Nervous System is the body's most rapid means of maintaining homeostasis (maintenance of constant internal environment)

Structural Classification of Nervous System

Central nervous system (CNS) (Fig 12.1)

Brain - 100 billion neurons (each synapse with 1,000 -10,000 other neurons)

Spinal Cord

Peripheral nervous system (PNS) - communication between CNS and rest of body (Fig 12.10)

Structural Divisions

Cranial nerves (12 pairs)

Spinal nerves (31 pairs)

Functional Divisions (uses both cranial and spinal nerves)

Somatic nervous system

Controls skeletal muscle
Voluntary

Autonomic nervous system

Sympathetic division (responds to short term stress)
Parasympathetic division (returns body to normal functions following stress)
Controls smooth muscle, cardiac muscle and glands
Involuntary

Enteric Nervous System

Controls smooth muscle and glands of the digestive system



Involuntary

Functional Classification of Nervous System

Sensory (Afferent) = Input - senses changes in external and internal environment & transmits changes via sensory neurons/afferent neurons to CNS

Integrative (Processing) - Interprets changes (solely in CNS)

Motor (Efferent) = Output - Responds to changes in form of muscular contraction/gland secretion via motor neurons/efferent neurons

Neurons

Neurons – specialize in conducting action potential (nerve impulse)

Amitotic but high rate of metabolism that requires abundant supply of O2 and glucose

Parts of a Neuron (Fig 12.2 & Table 12.3)

Cell body

Clustered into ganglia in PNS

Clustered into nuclei in brain

Clustered into horns in spinal cord

Contains nucleus

Contains Nissl bodies - rough ER - site of protein synthesis

Contains neurofibrils - cytoskeleton that extends into axons and dendrites and used to transport neurotransmitters, nutrients, etc

NOTE: herpes, rabies, and polio viruses and toxin from Clostridium tetani travels along neurofibrils of axons to cell bodies where they can multiply and cause damage

Dendrites

Extensions that receive information along with the cell body in motor neurons and interneurons or generate input in sensory neurons (once extension becomes myelinated, it is then called an axon) (Fig 12.4)

Axons

Conduct action potentials toward the axon terminal

Distal end of axons swell into synaptic end bulbs that contain neurotransmitters in synaptic vesicles

Bundles of neuron axons in CNS = tracts (axons bundled with neuroglia)

Bundles of neuron axons in PNS = nerves (axons bundled with endoneurium/perineurium/epineurium)

Frequently myelinated in both CNS and PNS

Structural Classification of Neurons

Structural classification: classification of neurons according to the number of process from the cell body (Fig 12.3, 12.4 & 12.5)

Unipolar neuron - one process from cell body

Sensory or afferent in function

Begins as a bipolar neuron in embryo but fuses into single extension

Bipolar neuron - 2 extensions from cell body

Examples: rods and cones (shapes of dendrites) of retina, olfactory neurons, inner ear neurons

Multipolar neuron - many extensions from cell body

Most of CNS (interneurons) and all motor neurons

Functional Classification of Neurons

Functional classification: classification according to the direction which impulses are conducted relative to the CNS (Fig 12.10)

Sensory (afferent) neuron - strictly PNS - transmit impulses toward CNS from receptors

Includes both unipolar and bipolar neurons

In unipolar neurons, cell bodies are just outside the spinal cord in a structure called the posterior (dorsal) root ganglia

Motor (efferent) neuron - transmits impulses away from CNS to muscles/glands

Cell bodies are in spinal cord

All are multipolar

Interneurons (association) neuron - all are found totally within the CNS

All are multipolar

Make up 90% of total neurons

Neuroglia = Glial cells

Neuroglia - support, connect, and protect the impulse conducting cells of the nervous system (neurons) in both CNS and PNS

Cancer of NS - (gliomas) involves neuroglia and not neurons because neuroglia have retained mitotic ability but neurons have not retained mitotic ability beyond infancy

Neuroglia outnumber neurons by 5 - 50 X

Neuroglia from CNS (Fig 12.6)

Astrocytes – star shaped

Twine around neurons to form supporting network
Attach neurons to blood vessels
Create blood-brain barrier
Produce "scar tissue" if there is damage to CNS

Microglia - derived from monocytes

Become phagocytic and remove injured brain or cord tissue

Ependymal cells - epithelial cells that line ventricles of brain and central canal of cord

Ciliated to assist in circulation of CSF

Oligodendrocytes - similar to astrocytes but have fewer extensions

Produce myelin sheath in CNS

Neuroglia from PNS (Fig 12.7)

Schwann cells - produce myelin sheath in PNS

Satellite cells - support cell bodies in PNS

Myelin Sheath

Myelin sheath produced around an axon by the following two neuroglia cells

Oligodendrocytes

CNS

Can myelinate up to 15 different neurons (axons)

Schwann cells

PNS

Can have up to 500 Schwann cells along the longest neurons (myelinate only one axon)

Myelin sheath = multilayered lipid and protein covering surrounding axons in PNS and CNS (actually multilayers of cell membrane from Schwann cell or extension from oligodendrocyte)

Myelin sheath electrically insulates the axon and increases speed of nerve impulse conduction (action potential)

Schwann cell wraps like a jelly roll so that up to 100 layers of the cell rolls around the axon

The outer part of the cell contains the nucleus and the Schwann cell membrane (Fig 12.8)

The Schwann cell membrane is called the neurolemma

Evidence has shown that the neurolemma aids in repair and regeneration of axons in the PNS (absent in CNS) (Fig 12.29)

Guillain-Barre Syndrome – demyelination of axons in the PNS by macrophages

macrophages destroy Schwann cells which can regenerate

person suffers from acute paralysis but most patients recover completely

Oligodendrocytes have "octopus-like extensions" that wrap several different axons and therefore do not have neurolemma (may be one reason why CNS neurons don't regenerate) (Fig 12.6)

Multiple Sclerosis - autoimmune disorder in which Killer T-cells destroy oligodendrocytes that are replaced by plaques (scleroses) from astrocytes

Interferes with impulse transmission
MS is also known as a demyelination disorder of the CNS

Nodes of Ranvier - gaps in myelinated neuron where myelin absent (Fig 12.2 & 12.7)

Nodes of Ranvier are produced by both Schwann cells as well as oligodendrocytes, so nodes of Ranvier are present in both CNS & PNS

White matter - cell processes (axons) with myelin (Fig 12.9)

Nerve fiber - general term for myelinated axon in both CNS and PNS

Gray matter - parts of neuron, especially cell bodies and dendrites, that lack myelin

Always located in protected areas of CNS

Ganglia would also be gray because cell bodies are not myelinated

Neurophysiology

Action potential - An electrical signal that propagates along the membrane of a neuron or muscle fiber

Neurophysiology = Excitability - ability to respond to a stimulus (stimulus – any condition capable of altering the cell’s membrane potential) and convert it into an action potential

Nerve conduction of action potentials involves an electrochemical mechanism

Ion Channels

Proteins in the cell membrane

Don’t require ATP - movement of ions is by channel-mediated facilitative diffusion (Fig 12.11 & Table 12.1)

Nongated

Leakage channels - randomly open

Cell membranes of muscle/neurons have more K+ leakage channels than Na+ leakage channels

Gated - channels open and close in response to some stimulus

Chemical (ligand) gated - open and close in response to chemicals like neurotransmitters, hormones, ions (dendrites and cell bodies)

Mechanically gated - open and close in response to mechanical vibration or pressure such as sound waves or pressure of touch/stretch (dendrites of sensory neurons)

Voltage gated - open and close in response to voltage (axons only)

Require ATP - movement of ions is by active transport

Na+K+ Pump (Na+K+ ATPase) - movement of three Na+ ions out of the cell and two K+ ions into the cell by active transport which requires ATP

Resting Membrane Potential (RMP)

Nonconducting neuron has a RMP of -70mV (Fig 12.12)

Reason for resting membrane potential (Fig 12.13)

The inside of the membrane has non-diffusible anions (-) (phosphate and protein anions)

K+ ions are more numerous on the inside than outside – Remember

Na+ and Cl- ions more numerous outside

Small amounts of K+ move to the outside through leakage (nongated) channels with anions following (cannot diffuse through the membrane and get stuck at the membrane)

Note: there are more K+ leakage channels than Na+ leakage channels

The inside of the cell has a more negative charge than the outside which is positive; overall the inside of the membrane is -70mV

Maintain resting membrane potential with Na+K+ Pump

Membrane is said to be polarized because of the difference in charge across the membrane = resting membrane potential

K+ is inside, Na+ is outside, Inside = (-)

All or None Principal

All or None Principle - Neuron transmits action potentials according to all or none principle

If the stimulus is strong enough to generate an action potential, the impulse is conducted down the neuron at a constant and maximum strength for the existing conditions

Stimulus must raise membrane potential to less negative than -55mV (Threshold potential) (Fig 12.19)

Graded Potentials

Graded potentials – local potentials (Table 12.2)

Affected at site of stimulation and effect decreases with distance

Spreads passively

The stronger the stimulus, the greater the change in potential and the larger area affected (Fig 12.16)

The potential change could be either negative or positive (Fig 12.14 & 12.15)

Excitatory stimulus - Increases Na+ into cell making membrane hypopolarized

Partially depolarizes and makes membrane less negative

Causes depolarization (but not to -55 mV)

Single excitatory stimulus usually does not initiate nerve impulse but membrane is closer to the threshold and more likely to reach threshold with next excitatory stimulus

Inhibitory stimulus - Increases K+ outward or increases Cl- inward

Makes membrane more negative

Makes the membrane hyperpolarized (as low as -90mV)

Generation of action potential is now more difficult

Must add up all the excitatory and inhibitory stimuli (summation) that are influencing the neuron to determine if an action potential will be sent (Fig 12.17 & 12.26)

Action Potentials

Action Potential (AP) = rapid change in membrane potential (polarity) that can spread down the length of the axon

The membrane will depolarize and then repolarize

Only muscle and neurons can produce an AP

In neurons, an AP lasts about 1 ms or less

Propagation of APs down axons = nerve impulses

Steps in generating an Action Potential (Fig 12.18 - 12.20)

1. Depolarization

When a stimulus is applied, if the sum of stimuli is excitatory (mechanical gated or chemical gated ion channels open and cause a net flow of Na+ into the cell) and depolarization occurs to threshold potential (threshold = -55mV)

At -55 mV, voltage gated Na+ channels open and Na+ rushes in (Na+ inflow), making the inside of the cell positive

This is the depolarization (Na+ inflow) phase = normal polarized state is reversed

Inside = (+)

K+ is inside, Na+ is inside, Inside = (+)

2. Repolarization - membrane potential returns to a negative value

Repolarization is due to K+ ions flowing outward (K+ outflow) through voltage gated K+ channels

Voltage gated Na+ channels inactivate and close

Voltage-gated K+ channels open in response to positive membrane and remain open until membrane potential returns to a negative value

Ion distribution is reverse of that at resting

Inside = (-)

K+ is outside, Na+ is inside, Inside = (-)

Refractory Period - period of time during which an excitable cell cannot generate another action potential

Voltage gated Na+ channels cannot reopen until they become reactivated
Because ion distribution has not returned to resting, sufficient potential has not built up on either side of the membrane to generate a new action potential
The refractory period begins at depolarization and continues until the resting membrane ion distribution is restored
The refractory period can be short (0.4 ms in skeletal muscle) because only a few Na+ rush in and only a few K+ move out with each nerve impulse

3. Restoration of Resting Membrane Potential

Leakage channels allow ions to flow into and out of the cell

The Na+K+ pump also operates in restoring the resting ion distribution by pumping Na+ out of the cell and K+ into the cell

K+ is inside, Na+ is outside, Inside = (-)

4. Propagation of Action Potentials (Fig 12.21)

Each action potential acts as a stimulus for development of another action potential in an adjacent segment of membrane

The Na+ inflow during the depolarization phase of an action potential diffuses to an adjacent membrane segment

Increase in Na+ concentration raises the membrane potential of that membrane segment to the threshold potential, generating a new action potential

Action potentials do not travel but are regenerated in sequence along an axon like tipping dominos

Refractory period prevents action potential from going backwards

Action potentials continue to be regenerated in sequence until the potential reaches the end of the axon

Saltatory Conduction

Saltatory conduction - Action potentials are only generated at the Nodes of Ranvier (Fig 12.21)

Action potential will skip from node to node

Ionic movement is inhibited beneath myelin sheath

Conserves energy because Na-K Pump is not needed as extensively because only Nodes of Ranvier are depolarized and repolarized

Conducts up to 50x faster than unmyelinated neuron

Speed of Impulse Conduction

Speed of impulse conduction (propagation) determined by:

Presence of myelin sheath - the further the nodes are apart, the faster the transmission

Diameter of fiber - the greater the diameter the greater density of voltage gated Na+ channels; the greater the diameter, the faster the transmission

Temperature - the greater the temperature the faster the transmission

Localized cooling can block impulse conduction; therefore pain can be reduced by application of ice

Types of nerve fibers based on transmission speed

A fibers - myelinated and large diameter; fastest conduction; in areas where split second responses can mean survival; speeds up to 280 mph

B fibers - myelinated and smaller diameter; speeds up to 32 mph

C fibers - unmyelinated and smaller diameter; speeds up to 4 mph

Note: B and C fibers are going to and from viscera

Synapse

Synapse - connection between axon terminal and another neuron, muscle (neuromuscular junction), or gland (neuroglandular junction)

Electrical synapse: ionic current spreads directly from one cell to another through gap junctions (found in cardiac and smooth muscle)

Chemical synapses: neurotransmitter is secreted from one cell and a second cell responds to it


Flow of information is in one direction

Structure of chemical synapse (Fig 12.22)

Synaptic end bulb of first neuron (presynaptic neuron) = presynaptic membrane

Presynaptic electrical signal is converted to chemical signal

Presynaptic neuron releases neurotransmitter

Synaptic cleft: 20-50 nm gap between neuron and next structure

Impulse cannot jump cleft, therefore, will need chemical transmission in form of neurotransmitter

Cell membrane of second neuron (postsynaptic neuron) = postsynaptic membrane

Postsynaptic neuron has receptors for neurotransmitter

Postsynaptic neuron receives chemical signal (neurotransmitter) and in turn may generate an electrical signal (action potential)

Exocytosis of neurotransmitter (Fig 12.23)

When nerve impulse (action potential) arrives at synaptic end bulb, the depolarization phase opens voltage gated Ca2+ channels

Extracellular Ca2+ flows inward

Increase in Ca2+ inside the neuron, triggers exocytosis of synaptic vesicles

Neurotransmitter enters synaptic cleft

Neurotransmitter can either be excitatory or inhibitory

inhibitory neurotransmitters prevents chaos in nervous system

Neurotransmitters have to be inactivated or transported back into the presynaptic neuron

neurotransmitters must be removed from cleft

Neurotransmitters interact with receptor sites of chemically gated ion channels on the postsynaptic membrane to produce:

EPSP – excitatory postsynaptic potential - a type of graded potential (Fig 12.24)


Typically results from the opening of chemically gated Na+ channels.

IPSP - inhibitory postsynaptic potential - a type of graded potential


Typically results from the opening of chemically gated K+ channels or Cl- channels.

Summation of EPSP & IPSP = inhibition or excitation

Spatial (multiple synapse stimulation) (Fig 12.25)

Temporal (time)

Integration of EPSP and IPSP is at axon hillock (trigger zone)

Whether a neurotransmitter is excitatory or inhibitory is determined by the postsynaptic membrane receptor

Must have a mechanism to remove neurotransmitters from synaptic cleft to be able to turn signal off

Neurotransmitters

At least 75 neurotransmitters (Fig 12.27)

Acetylcholine (ACh) - main neurotransmitter of PNS (not common in CNS)

Excitatory for skeletal muscle

Inhibitory for cardiac muscle

Important in brain for memory consolidation (destroyed in Alzheimer’s)

Adenosine – excitatory in PNS and CNS

Caffeine acts as a competitive inhibitor at adenosine receptors in the brain

Catecholamines

Affect mood

6-C ringed structure with 2 hydroxyl groups and an attached amine

They are degraded by catechol-O-methyltransferase and monoamine oxidase (MAO)

Dopamine (DA)

DA is secreted in specific parts of the brain

Excitatory for emotional response but inhibitory in motor functions

Low levels are associated with Parkinson's

Excess DA associated with schizophrenia

DA seems to be the neurotransmitter involved in addiction to heroin, methamphetamines, cocaine, marijuana, alcohol, nicotine, caffeine

Cocaine prevents DA reuptake

Norepinephrine (NE)

Found in brain and secreted by sympathetic nervous system

Affects mood

Low levels are associated with depression

Methamphetamines (speed) - prevents NE reuptake

Epinephrine = adrenaline

Secreted by the adrenal gland

Enhances sympathetic nervous system response

Serotonin

Produced from amino acid, tryptophan

High amts in milk and turkey

Serotonin is secreted in parts of the brain and spinal cord

Affects mood

Induces sleep

Aids in memory

Prozac, Paxil, Zoloft, Luvox, Celexa and Lexapro inhibit its reuptake by the presynaptic membrane

LSD blocks the activity of serotonin

Ecstasy inhibits its reuptake by the presynaptic terminal and induces the presynaptic neuron to release even more serotonin

Ecstasy also induces the release of norepinephrine and dopamine

Amino acids and Amino acid like compounds

Glycine

Common inhibitory neurotransmitter in spinal cord (1/2 of inhibitory synapses in cord use glycine)

Tetanus toxin inhibits glycine, causing "lockjaw“

Strychnine blocks glycine receptors, causing the diaphragm to continuously contract which leads to suffocation

GABA (Gamma aminobutyric acid)

1/2 of inhibitory synapses in spinal cord use GABA

Common inhibitory neurotransmitter in brain (as many as 1/3 of brain synapses use GABA)

Prevents chaos in nervous system

GABA reduces anxiety

Valium, Xanax, alcohol and barbituates enhance the action of GABA

Treatment for epilepsy is drug that increases GABA

Glutamate (Glutamic acid)

Common excitatory in CNS

Increase in glutamate after stroke may lead to death of neurons because of oxygen deprivation to glutamate transporters that work by active transport (requires oxygen for ATP synthesis)

Asparagine (Aspartic acid)

Common excitatory in CNS

Peptides - series of covalently linked amino acids (Table 12.4)

Substance P - neurotransmitter in pain pathways (mediates our perception of pain)

Enkephalins and endorphins - endogenous morphine-like substances

Both are structurally similar to morphine and bind to morphine receptors

Modulate pain by inhibiting release of substance P

Runner’s high

Natural child birth

Certain disorders such as Parkinson's disease, Alzheimer's disease, depression, anxiety, schizophrenia involves problems relating to neurotransmitters

Circuits

Circuits (Fig 12.28)

Typical neuron receives input from 1,000 to 10,000 synapses

Each presynaptic neuron may branch and synapse with up to 25,000 or more different postsynaptic neurons

Convergence - single postsynaptic neuron controlled by converging signals coming from 2 or more presynaptic neurons

Divergence - single presynaptic neuron stimulates many different postsynaptic neurons



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