Chapter 12

Principles of Human Anatomy and Physiology, 11e 1

Chapter 12

Nervous Tissue

Lecture Outline


INTRODUCTION

• The nervous system, along with the endocrine system, helps to keep controlled conditions within limits that maintain health and helps to maintain homeostasis.

• The nervous system is responsible for all our behaviors, memories, and movements.

• The branch of medical science that deals with the normal functioning and disorders of the nervous system is called neurology.


Chapter 12Nervous Tissue

• Controls and integrates all body activities within limits that maintain life

• Three basic functions– sensing changes with sensory receptors

• fullness of stomach or sun on your face– interpreting and remembering those changes– reacting to those changes with effectors

• muscular contractions• glandular secretions


Major Structures of the Nervous System

• Brain, cranial nerves, spinal cord, spinal nerves, ganglia, enteric plexuses and sensory receptors


Structures of the Nervous System - Overview

• Twelve pairs of cranial nerves emerge from the base of the brain through foramina of the skull.– A nerve is a bundle of hundreds or thousands of axons, each of

which courses along a defined path and serves a specific region of the body.

• The spinal cord connects to the brain through the foramen magnum of the skull and is encircled by the bones of the vertebral column.– Thirty-one pairs of spinal nerves emerge from the spinal cord, each

serving a specific region of the body.• Ganglia, located outside the brain and spinal cord, are small masses of

nervous tissue, containing primarily cell bodies of neurons.• Enteric plexuses help regulate the digestive system.• Sensory receptors are either parts of neurons or specialized cells that

monitor changes in the internal or external environment.


Functions of the Nervous Systems

• The sensory function of the nervous system is to sense changes in the internal and external environment through sensory receptors. – Sensory (afferent) neurons serve this function.

• The integrative function is to analyze the sensory information, store some aspects, and make decisions regarding appropriate behaviors. – Association or interneurons serve this function.

• The motor function is to respond to stimuli by initiating action. – Motor(efferent) neurons serve this function.


Nervous System Divisions

• Central nervous system (CNS) – consists of the brain and spinal cord

• Peripheral nervous system (PNS)– consists of cranial and spinal nerves that contain both

sensory and motor fibers– connects CNS to muscles, glands & all sensory receptors


Subdivisions of the PNS• Somatic (voluntary) nervous system (SNS)

– neurons from cutaneous and special sensory receptors to the CNS

– motor neurons to skeletal muscle tissue• Autonomic (involuntary) nervous systems

– sensory neurons from visceral organs to CNS– motor neurons to smooth & cardiac muscle and glands

• sympathetic division (speeds up heart rate)• parasympathetic division (slow down heart rate)

• Enteric nervous system (ENS)– involuntary sensory & motor neurons control GI tract– neurons function independently of ANS & CNS


Organization of the Nervous System

• CNS is brain and spinal cord• PNS is everything else


Enteric NS

• The enteric nervous system (ENS) consists of neurons in enteric plexuses that extend the length of the GI tract.– Many neurons of the enteric plexuses function

independently of the ANS and CNS.– Sensory neurons of the ENS monitor chemical changes

within the GI tract and stretching of its walls, whereas enteric motor neurons govern contraction of GI tract organs, and activity of the GI tract endocrine cells.


HISTOLOGY OF THE NERVOUS SYSTEM


Neuronal Structure & Function


Neurons• Functional unit of nervous system• Have capacity to produce action potentials

– electrical excitability• Cell body

– single nucleus with prominent nucleolus– Nissl bodies (chromatophilic substance)

• rough ER & free ribosomes for protein synthesis

– neurofilaments give cell shape and support– microtubules move material inside cell– lipofuscin pigment clumps (harmless aging)

• Cell processes = dendrites & axons


Nucleus with Nucleolus

Parts of a Neuron

Axons or Dendrites

Cell body

Neuroglial cells


Cell membrane

• The dendrites are the receiving or input portions of a neuron.

• The axon conducts nerve impulses from the neuron to the dendrites or cell body of another neuron or to an effector organ of the body (muscle or gland).


Dendrites

• Conducts impulses towards the cell body

• Typically short, highly branched & unmyelinated

• Surfaces specialized for contact with other neurons

• Contains neurofibrils & Nissl bodies


Axons• Conduct impulses away

from cell body• Long, thin cylindrical

process of cell • Arises at axon hillock • Impulses arise from initial

segment (trigger zone)• Side branches

(collaterals) end in fine processes called axon terminals

• Swollen tips called synaptic end bulbs contain vesicles filled with neurotransmitters

Synaptic boutons


Axonal Transport

• Cell body is location for most protein synthesis– neurotransmitters & repair proteins

• Axonal transport system moves substances – slow axonal flow

• movement in one direction only -- away from cell body• movement at 1-5 mm per day

– fast axonal flow• moves organelles & materials along surface of

microtubules• at 200-400 mm per day• transports in either direction• for use or for recycling in cell body


Axonal Transport & Disease

• Fast axonal transport route by which toxins or pathogens reach neuron cell bodies– tetanus (Clostridium tetani bacteria)– disrupts motor neurons causing painful muscle

spasms• Bacteria enter the body through a laceration or

puncture injury– more serious if wound is in head or neck because

of shorter transit time


Diversity in Neurons

• Both structural and functional features are used to classify the various neurons in the body.

• On the basis of the number of processes extending from the cell body (structure), neurons are classified as multipolar, biopolar, and unipolar (Figure 12.4).

• Most neurons in the body are interneurons and are often named for the histologist who first described them or for an aspect of their shape or appearance. Examples are Purkinje cells (Figure 12.5a) or Renshaw cells (Figure 12.5b).


Structural Classification of Neurons

• Based on number of processes found on cell body– multipolar = several dendrites & one axon

• most common cell type– bipolar neurons = one main dendrite & one axon

• found in retina, inner ear & olfactory – unipolar neurons = one process only(develops from a bipolar)

• are always sensory neurons


Functional Classification of Neurons

• Sensory (afferent) neurons– transport sensory information from skin, muscles,

joints, sense organs & viscera to CNS• Motor (efferent) neurons

– send motor nerve impulses to muscles & glands• Interneurons (association) neurons

– connect sensory to motor neurons– 90% of neurons in the body


Association or Interneurons


• Half of the volume of the CNS • Smaller cells than neurons• 50X more numerous• Cells can divide

– rapid mitosis in tumor formation (gliomas)• 4 cell types in CNS

– astrocytes, oligodendrocytes, microglia & ependymal• 2 cell types in PNS

– schwann and satellite cells

Neuroglial Cells


Astrocytes

• Star-shaped cells• Form blood-brain barrier

by covering blood capillaries

• Metabolize neurotransmitters

• Regulate K+ balance• Provide structural

support


Microglia

• Small cells found near blood vessels

• Phagocytic role -- clear away dead cells

• Derived from cells that also gave rise to macrophages & monocytes


Ependymal cells

• Form epithelial membrane lining cerebral cavities & central canal

• Produce cerebrospinal fluid (CSF)


Satellite Cells

• Flat cells surrounding neuronal cell bodies in peripheral ganglia

• Support neurons in the PNS ganglia


Oligodendrocytes

• Most common glial cell type

• Each forms myelin sheath around more than one axons in CNS

• Analogous to Schwann cells of PNS


Myelination

• A multilayered lipid and protein covering called the myelin sheath and produced by Schwann cells and oligodendrocytes surrounds the axons of most neurons (Figure 12.8a).

• The sheath electrically insulates the axon and increases the speed of nerve impulse conduction.


Schwann Cell

• Cells encircling PNS axons• Each cell produces part of the myelin sheath

surrounding an axon in the PNS


Axon Coverings in PNS• All axons surrounded by a lipid & protein

covering (myelin sheath) produced by Schwann cells

• Neurilemma is cytoplasm & nucleusof Schwann cell– gaps called nodes of Ranvier

• Myelinated fibers appear white– jelly-roll like wrappings made of

lipoprotein = myelin– acts as electrical insulator– speeds conduction of nerve impulses

• Unmyelinated fibers– slow, small diameter fibers– only surrounded by neurilemma but no

myelin sheath wrapping


Myelination in PNS

• Schwann cells myelinate (wrap around) axons in the PNS during fetal development

• Schwann cell cytoplasm & nucleus forms outermost layer of neurolemma with inner portion being the myelin sheath

• Tube guides growing axons that are repairing themselves


Myelination in the CNS• Oligodendrocytes myelinate axons in the CNS • Broad, flat cell processes wrap about CNS axons, but the

cell bodies do not surround the axons• No neurilemma is formed• Little regrowth after injury is possible due to the lack of a

distinct tube or neurilemma


Gray and White Matter

• White matter = myelinated processes (white in color)• Gray matter = nerve cell bodies, dendrites, axon terminals,

bundles of unmyelinated axons and neuroglia (gray color)– In the spinal cord = gray matter forms an H-shaped inner

core surrounded by white matter– In the brain = a thin outer shell of gray matter covers the

surface & is found in clusters called nuclei inside the CNS• A nucleus is a mass of nerve cell bodies and dendrites inside

the CNS.


Electrical Signals in Neurons

• Neurons are electrically excitable due to the voltage difference across their membrane

• Communicate with 2 types of electric signals– action potentials that can travel long distances– graded potentials that are local membrane

changes only• In living cells, a flow of ions occurs through ion

channels in the cell membrane


Two Types of Ion Channels

• Leakage (nongated) channels are always open– nerve cells have more K+ than Na+ leakage channels – as a result, membrane permeability to K+ is higher– explains resting membrane potential of -70mV in nerve

tissue• Gated channels open and close in response to a stimulus

– results in neuron excitability


Ion Channels

• Gated ion channels respond to voltage changes, ligands (chemicals), and mechanical pressure.– Voltage-gated channels respond to a direct change in the

membrane potential (Figure 12.10a).– Ligand-gated channels respond to a specific chemical

stimulus (Figure 12.10b).– Mechanically gated ion channels respond to mechanical

vibration or pressure.


Gated Ion Channels


Resting Membrane Potential

• Negative ions along inside of cell membrane & positive ions along outside– potential energy difference at rest is -70 mV – cell is “polarized”

• Resting potential exists because– concentration of ions different inside & outside

• extracellular fluid rich in Na+ and Cl• cytosol full of K+, organic phosphate & amino acids

– membrane permeability differs for Na+ and K+• 50-100 greater permeability for K+• inward flow of Na+ can’t keep up with outward flow of K+• Na+/K+ pump removes Na+ as fast as it leaks in



Graded Potentials

• Small deviations from resting potential of -70mV– hyperpolarization = membrane

has become more negative– depolarization = membrane has

become more positive

• The signals are graded, meaning they vary in amplitude (size), depending on the strength of the stimulus and localized.

• Graded potentials occur most often in the dendrites and cell body of a neuron.


How do Graded Potentials Arise?

• Source of stimuli– mechanical stimulation of membranes with mechanical

gated ion channels (pressure)– chemical stimulation of membranes with ligand gated ion

channels (neurotransmitter)• Graded/postsynaptic/receptor or generator potential

– ions flow through ion channels and change membrane potential locally

– amount of change varies with strength of stimuli• Flow of current (ions) is local change only


Generation of an Action Potential

• An action potential (AP) or impulse is a sequence of rapidly occurring events that decrease and eventually reverse the membrane potential (depolarization) and then restore it to the resting state (repolarization). – During an action potential, voltage-gated Na+ and K+

channels open in sequence (Figure 12.13).• According to the all-or-none principle, if a stimulus reaches

threshold, the action potential is always the same. – A stronger stimulus will not cause a larger impulse.


Action Potential

• Series of rapidly occurring events that change and then restore the membrane potential of a cell to its resting state

• Ion channels open, Na+ rushes in (depolarization), K+ rushes out (repolarization)

• All-or-none principal = with stimulation, either happens one specific way or not at all (lasts 1/1000 of a second)

• Travels (spreads) over surface of cell without dying out


Depolarizing Phase of Action Potential

• Chemical or mechanical stimuluscaused a graded potential to reachat least (-55mV or threshold)

• Voltage-gated Na+ channels open& Na+ rushes into cell– in resting membrane, inactivation gate of sodium channel is open &

activation gate is closed (Na+ can not get in)– when threshold (-55mV) is reached, both open & Na+ enters– inactivation gate closes again in few ten-thousandths of second– only a total of 20,000 Na+ actually enter the cell, but they change

the membrane potential considerably(up to +30mV)• Positive feedback process


Repolarizing Phase of Action Potential

• When threshold potential of-55mV is reached, voltage-gated K+ channels open

• K+ channel opening is muchslower than Na+ channelopening which caused depolarization

• When K+ channels finally do open, the Na+ channels have already closed (Na+ inflow stops)

• K+ outflow returns membrane potential to -70mV• If enough K+ leaves the cell, it will reach a -90mV membrane

potential and enter the after-hyperpolarizing phase• K+ channels close and the membrane potential returns to the

resting potential of -70mV


Refractory Period of Action Potential

• Period of time during whichneuron can not generateanother action potential

• Absolute refractory period– even very strong stimulus will

not begin another AP– inactivated Na+ channels must return to the resting state

before they can be reopened– large fibers have absolute refractory period of 0.4 msec and up

to 1000 impulses per second are possible• Relative refractory period

– a suprathreshold stimulus will be able to start an AP– K+ channels are still open, but Na+ channels have closed


The Action Potential: Summarized

• Resting membrane potential is -70mV

• Depolarization is the change from -70mV to +30 mV

• Repolarization is the reversal from +30 mV back to -70 mV)


Local Anesthetics

• Local anesthetics and certain neurotoxins– Prevent opening of voltage-gated Na+ channels– Nerve impulses cannot pass the anesthetized region

Examples:– Novocaine and lidocaine


Propagation of Action Potential

• An action potential spreads (propagates) over the surface of the axon membrane– as Na+ flows into the cell during depolarization, the

voltage of adjacent areas is effected and their voltage-gated Na+ channels open

– self-propagating along the membrane• The traveling action potential is called a nerve impulse


Continuous versus Saltatory Conduction

• Continuous conduction (unmyelinated fibers)– step-by-step depolarization of each portion of the

length of the axolemma• Saltatory conduction

– depolarization only at nodes of Ranvier where there is a high density of voltage-gated ion channels

– current carried by ions flows through extracellular fluid from node to node


Saltatory Conduction

• Nerve impulse conduction in which the impulse jumps from node to node


Speed of Impulse Propagation

• The propagation speed of a nerve impulse is not related to stimulus strength. – larger, myelinated fibers conduct impulses faster due to size

& saltatory conduction • Fiber types

– A fibers largest (5-20 microns & 130 m/sec)

• myelinated somatic sensory & motor to skeletal muscle– B fibers medium (2-3 microns & 15 m/sec)

• myelinated visceral sensory & autonomic preganglionic– C fibers smallest (.5-1.5 microns & 2 m/sec)

• unmyelinated sensory & autonomic motor


Encoding of Stimulus Intensity

• How do we differentiate a light touch from a firmer touch?– frequency of impulses

• firm pressure generates impulses at a higher frequency

– number of sensory neurons activated• firm pressure stimulates more neurons than does a

light touch


Action Potentials in Nerve and Muscle

• Entire muscle cell membrane versus only the axon of the neuron is involved

• Resting membrane potential– nerve is -70mV– skeletal & cardiac muscle is closer to -90mV

• Duration– nerve impulse is 1/2 to 2 msec– muscle action potential lasts 1-5 msec for skeletal & 10-

300msec for cardiac & smooth• Fastest nerve conduction velocity is 18 times faster than

velocity over skeletal muscle fiber


SIGNAL TRANSMISSION AT SYNAPSES

• A synapse is the functional junction between one neuron and another or between a neuron and an effector such as a muscle or gland.


Signal Transmission at Synapses

• 2 Types of synapses– electrical

• ionic current spreads to next cell through gap junctions• faster, two-way transmission & capable of

synchronizing groups of neurons– chemical

• one-way information transfer from a presynaptic neuron to a postsynaptic neuron

– axodendritic -- from axon to dendrite– axosomatic -- from axon to cell body– axoaxonic -- from axon to axon



Chemical Synapses

• Action potential reaches end bulb and voltage-gated Ca+ 2 channels open

• Ca+2 flows inward triggering release of neurotransmitter

• Neurotransmitter crosses synaptic cleft & binding to ligand-gated receptors – the more neurotransmitter

released the greater the change in potential of the postsynaptic cell

• Synaptic delay is 0.5 msec• One-way information transfer


Excitatory & Inhibitory Potentials

• The effect of a neurotransmitter can be either excitatory or inhibitory– a depolarizing postsynaptic potential is called an EPSP

• it results from the opening of ligand-gated Na+ channels

• the postsynaptic cell is more likely to reach threshold– an inhibitory postsynaptic potential is called an IPSP

• it results from the opening of ligand-gated Cl- or K+ channels

• it causes the postsynaptic cell to become more negative or hyperpolarized

• the postsynaptic cell is less likely to reach threshold


Removal of Neurotransmitter

• Diffusion– move down concentration

gradient• Enzymatic degradation

– acetylcholinesterase• Uptake by neurons or glia cells

– neurotransmitter transporters

– Prozac = serotonin reuptake

inhibitor


Three Possible Responses

• Small EPSP occurs– potential reaches -56 mV only

• An impulse is generated– threshold was reached– membrane potential of at least -55 mV

• IPSP occurs– membrane hyperpolarized– potential drops below -70 mV


• Origin– GPs arise on dendrites and cell bodies– APs arise only at trigger zone on axon hillock

• Types of Channels– AP is produced by voltage-gated ion channels– GP is produced by ligand or mechanically-gated

channels • Conduction

– GPs are localized (not propagated)– APs conduct over the surface of the axon

Comparison of Graded & Action Potentials


Comparison of Graded & Action Potentials

• Amplitude– amplitude of the AP is constant (all-or-none)– graded potentials vary depending upon stimulus

• Duration– The duration of the GP is as long as the stimulus

lasts• Refractory period

– The AP has a refractory period due to the nature of the voltage-gated channels, and the GP has none.


Summation

• If several presynaptic end bulbs release their neurotransmitter at about the same time, the combined effect may generate a nerve impulse due to summation

• Summation may be spatial or temporal.


• Summation of effects of neurotransmitters released from several end bulbs onto one neuron

Spatial Summation


Temporal Summation

• Summation of effect of neurotransmitters released from 2 or more firings of the same end bulb in rapid succession onto a second neuron


Summation

• The postsynaptic neuron is an integrator, receiving and integrating signals, then responding.

• If the excitatory effect is greater than the inhibitory effect but less that the threshold level of stimulation, the result is a subthreshold EPSP, making it easier to generate a nerve impulse.

• If the excitatory effect is greater than the inhibitory effect and reaches or surpasses the threshold level of stimulation, the result is a threshold or suprathreshold EPSP and a nerve impulse.

• If the inhibitory effect is greater than the excitatory effect, the membrane hyperpolarizes (IPSP) with failure to produce a nerve impulse.


Neurotransmitters

• Both excitatory and inhibitory neurotransmitters are present in the CNS and PNS; the same neurotransmitter may be excitatory in some locations and inhibitory in others.

• Important neurotransmitters include acetylcholine, glutamate, aspartate, gamma aminobutyric acid, glycine, norepinephrine, epinephrine, and dopamine.


Neurotransmitter Effects

• Neurotransmitter effects can be modified– synthesis can be stimulated or inhibited– release can be blocked or enhanced– removal can be stimulated or blocked – receptor site can be blocked or activated

• Agonist– anything that enhances a transmitters effects

• Antagonist– anything that blocks the action of a neurotranmitter


Small-Molecule Neurotransmitters

• Acetylcholine (ACh)– released by many PNS neurons & some CNS– excitatory on NMJ but inhibitory at others– inactivated by acetylcholinesterase

• Amino Acids– glutamate released by nearly all excitatory neurons in

the brain ---- inactivated by glutamate specific transporters

– GABA is inhibitory neurotransmitter for 1/3 of all brain synapses (Valium is a GABA agonist -- enhancing its inhibitory effect)


• Biogenic Amines– modified amino acids (tyrosine)

• norepinephrine -- regulates mood, dreaming, awakening from deep sleep

• dopamine -- regulating skeletal muscle tone• serotonin -- control of mood, temperature

regulation, & induction of sleep– removed from synapse & recycled or destroyed by

enzymes (monoamine oxidase or catechol-0-methyltransferase)



• ATP and other purines (ADP, AMP & adenosine)– excitatory in both CNS & PNS– released with other neurotransmitters (ACh & NE)

• Gases (nitric oxide or NO)– formed from amino acid arginine by an enzyme– formed on demand and acts immediately

• diffuses out of cell that produced it to affect neighboring cells

• may play a role in memory & learning– first recognized as vasodilator that helps lower blood

pressure



Neuropeptides

• 3-40 amino acids linked by peptide bonds• Substance P -- enhances our perception of pain• Pain relief

– enkephalins -- pain-relieving effect by blocking the release of substance P

– acupuncture may produce loss of pain sensation because of release of opioids-like substances such as endorphins or dynorphins


Strychnine Poisoning

• In spinal cord, Renshaw cells normally release an inhibitory neurotransmitter (glycine) onto motor neurons preventing excessive muscle contraction

• Strychnine binds to and blocks glycine receptors in the spinal cord

• Massive tetanic contractions of all skeletal muscles are produced– when the diaphragm contracts & remains contracted,

breathing can not occur


Neuronal Circuits

• Neuronal pools are organized into circuits (neural networks.) These include simple series, diverging, converging, reverberating, and parallel after-discharge circuits (Figure 12.18 a-d).

• A neuronal network may contain thousands or even millions of neurons.

• Neuronal circuits are involved in many important activities– breathing – short-term memory– waking up


Neuronal Circuits• Diverging -- single cell stimulates many others• Converging -- one cell stimulated by many others• Reverberating -- impulses from later cells repeatedly stimulate

early cells in the circuit (short-term memory)• Parallel-after-discharge -- single cell stimulates a group of cells

that all stimulate a common postsynaptic cell (math problems)


Regeneration & Repair

• Plasticity maintained throughout life– sprouting of new dendrites– synthesis of new proteins– changes in synaptic contacts with other neurons

• Limited ability for regeneration (repair)– PNS can repair damaged dendrites or axons– CNS no repairs are possible


Damage and Repair in the Peripheral Nervous System (Figure 19.a)

• When there is damage to an axon, usually there are changes, called chromatolysis, which occur in the cell body of the affected cell; this causes swelling of the cell body and peaks between 10 and 20 days after injury.

• By the third to fifth day, degeneration of the distal portion of the neuronal process and myelin sheath (Wallerian degeneration) occurs; afterward, macrophages phagocytize the remains.

• Retrograde degeneration of the proximal portion of the fiber extends only to the first neurofibral node.

• Regeneration follows chromatolysis; synthesis of RNA and protein accelerates, favoring rebuilding of the axon and often taking several months.


• Axons & dendrites may be repaired if– neuron cell body remains intact– schwann cells remain active and

form a tube – scar tissue does not form too rapidly

• Chromatolysis– 24-48 hours after injury, Nissl

bodies break up into fine granular masses

Repair within the PNS


• By 3-5 days, – wallerian degeneration occurs

(breakdown of axon & myelin sheath distal to injury)

– retrograde degeneration occurs back one node

• Within several months, regeneration occurs– neurolemma on each side of injury

repairs tube (schwann cell mitosis)– axonal buds grow down the tube to

reconnect (1.5 mm per day)

Repair within the PNS


Neurogenesis in the CNS

• Formation of new neurons from stem cells was not thought to occur in humans– 1992 a growth factor was found that stimulates adult

mice brain cells to multiply– 1998 new neurons found to form within adult human

hippocampus (area important for learning)• There is a lack of neurogenesis in other regions of the

brain and spinal cord.• Factors preventing neurogenesis in CNS

– inhibition by neuroglial cells, absence of growth stimulating factors, lack of neurolemmas, and rapid formation of scar tissue


Multiple Sclerosis (MS)

• Autoimmune disorder causing destruction of myelin sheaths in CNS– sheaths becomes scars or plaques– 1/2 million people in the United States– appears between ages 20 and 40 – females twice as often as males

• Symptoms include muscular weakness, abnormal sensations or double vision

• Remissions & relapses result in progressive, cumulative loss of function


• The second most common neurological disorder – affects 1% of population

• Characterized by short, recurrent attacks initiated by electrical discharges in the brain– lights, noise, or smells may be sensed– skeletal muscles may contract involuntarily– loss of consciousness

• Epilepsy has many causes, including;– brain damage at birth, metabolic disturbances,

infections, toxins, vascular disturbances, head injuries, and tumors

Epilepsy


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