Chapter 11

The Nervous System and Nervous Tissue

Functions of the Nervous System

1. Sensory input

• Information gathered by sensory receptors about internal and external changes

2. Integration

• Interpretation of sensory input

3. Motor output

• Activation of effector organs (muscles and glands) produces a response

Figure 11.1

Sensory input

Motor output

Integration

Divisions of the Nervous System

• Central nervous system (CNS)

• Brain and spinal cord

• Integration and command center

• Peripheral nervous system (PNS)

• Paired spinal and cranial nerves carry messages to and from the CNS

Peripheral Nervous System (PNS)

• Two functional divisions

1. Sensory (afferent) division

• Somatic afferent fibers—convey impulses from skin, skeletal muscles, and joints

• Visceral afferent fibers—convey impulses from visceral organs

2. Motor (efferent) division

• Transmits impulses from the CNS to effector organs

Motor Division of PNS

1. Somatic (voluntary) nervous system

• Conscious control of skeletal muscles

Motor Division of PNS

2. Autonomic (involuntary) nervous system (ANS)

• Visceral motor nerve fibers

• Regulates smooth muscle, cardiac muscle, and glands

• Two functional subdivisions

• Sympathetic

• Parasympathetic

Figure 11.2

Central nervous system (CNS)

Brain and spinal cordIntegrative and control centers

Peripheral nervous system (PNS)

Cranial nerves and spinal nervesCommunication lines between theCNS and the rest of the body

Parasympatheticdivision

Conserves energyPromotes house-keeping functionsduring rest

Motor (efferent) division

Motor nerve fibersConducts impulses from the CNSto effectors (muscles and glands)

Sensory (afferent) divisionSomatic and visceral sensorynerve fibersConducts impulses fromreceptors to the CNS

Somatic nervoussystem

Somatic motor(voluntary)Conducts impulsesfrom the CNS toskeletal muscles

Sympathetic divisionMobilizes bodysystems during activity

Autonomic nervoussystem (ANS)

Visceral motor(involuntary)Conducts impulsesfrom the CNS tocardiac muscles,smooth muscles,and glands

StructureFunctionSensory (afferent)division of PNS Motor (efferent) division of PNS

Somatic sensoryfiber

Visceral sensory fiber

Motor fiber of somatic nervous system

Skin

StomachSkeletalmuscle

Heart

BladderParasympathetic motor fiber of ANS

Sympathetic motor fiber of ANS

Histology of Nervous Tissue

• Two principal cell types

1. Neurons—excitable cells that transmit electrical signals

Histology of Nervous Tissue

2. Neuroglia (glial cells)—supporting cells:

• Astrocytes (CNS)

• Microglia (CNS)

• Ependymal cells (CNS)

• Oligodendrocytes (CNS)

• Satellite cells (PNS)

• Schwann cells (PNS)

Astrocytes

• Most abundant, versatile, and highly branched glial cells

• Cling to neurons, synaptic endings, and capillaries

• Support and brace neurons

Astrocytes

• Help determine capillary permeability

• Guide migration of young neurons

• Control the chemical environment

• Participate in information processing in the brain

Figure 11.3a

(a) Astrocytes are the most abundantCNS neuroglia.

Capillary

Neuron

Astrocyte

Microglia

• Small, ovoid cells with thorny processes

• Migrate toward injured neurons

• Phagocytize microorganisms and neuronal debris

Figure 11.3b

(b) Microglial cells are defensive cells inthe CNS.

NeuronMicroglialcell

Ependymal Cells

• Range in shape from squamous to columnar

• May be ciliated

• Line the central cavities of the brain and spinal column

• Separate the CNS interstitial fluid from the cerebrospinal fluid in the cavities

Figure 11.3c

Brain orspinal cordtissue

Ependymalcells

Fluid-filled cavity

(c) Ependymal cells line cerebrospinalfluid-filled cavities.

Oligodendrocytes

• Branched cells

• Processes wrap CNS nerve fibers, forming insulating myelin sheaths

Figure 11.3d

(d) Oligodendrocytes have processes that formmyelin sheaths around CNS nerve fibers.

Nervefibers

Myelin sheath

Process ofoligodendrocyte

Satellite Cells and Schwann Cells

• Satellite cells

• Surround neuron cell bodies in the PNS

• Schwann cells (neurolemmocytes)

• Surround peripheral nerve fibers and form myelin sheaths

• Vital to regeneration of damaged peripheral nerve fibers

Figure 11.3e

(e) Satellite cells and Schwann cells (whichform myelin) surround neurons in the PNS.

Schwann cells(forming myelin sheath)

Cell body of neuronSatellitecells

Nerve fiber

Neurons (Nerve Cells)

• Special characteristics:

• Long-lived ( 100 years or more)

• Amitotic—with few exceptions

• High metabolic rate—depends on continuous supply of oxygen and glucose

• Plasma membrane functions in:

• Electrical signaling

• Cell-to-cell interactions during development

Cell Body (Perikaryon or Soma)

• Biosynthetic center of a neuron

• Spherical nucleus with nucleolus

•Well-developed Golgi apparatus

• Rough ER called Nissl bodies (chromatophilic substance)

Cell Body (Perikaryon or Soma)

• Network of neurofibrils (neurofilaments)

• Axon hillock—cone-shaped area from which axon arises

• Clusters of cell bodies are called nuclei in the CNS, ganglia in the PNS

Figure 11.4b

Dendrites(receptive regions)

Cell body(biosynthetic centerand receptive region)

Nucleolus

Nucleus

Nissl bodies

Axon(impulse generatingand conducting region)

Axon hillock

NeurilemmaTerminalbranches

Node of Ranvier

Impulsedirection

Schwann cell(one inter-node)

Axonterminals(secretoryregion)

(b)

Processes

• Dendrites and axons

• Bundles of processes are called

• Tracts in the CNS

• Nerves in the PNS

Dendrites

• Short, tapering, and diffusely branched

• Receptive (input) region of a neuron

• Convey electrical signals toward the cell body as graded potentials

The Axon

• One axon per cell arising from the axon hillock

• Long axons (nerve fibers)

• Occasional branches (axon collaterals)

The Axon

• Numerous terminal branches (telodendria)

• Knoblike axon terminals (synaptic knobs or boutons)

• Secretory region of neuron

• Release neurotransmitters to excite or inhibit other cells

Axons: Function

• Conducting region of a neuron

• Generates and transmits nerve impulses (action potentials) away from the cell body

Axons: Function

• Molecules and organelles are moved along axons by motor molecules in two directions:

• Anterograde—toward axonal terminal

• Examples: mitochondria, membrane components, enzymes

• Retrograde—toward the cell body

• Examples: organelles to be degraded, signal molecules, viruses, and bacterial toxins

Figure 11.4b

Dendrites(receptive regions)

Cell body(biosynthetic centerand receptive region)

Nucleolus

Nucleus

Nissl bodies

Axon(impulse generatingand conducting region)

Axon hillock

NeurilemmaTerminalbranches

Node of Ranvier

Impulsedirection

Schwann cell(one inter-node)

Axonterminals(secretoryregion)

(b)

Myelin Sheath

• Segmented protein-lipoid sheath around most long or large-diameter axons

• It functions to:

• Protect and electrically insulate the axon

• Increase speed of nerve impulse transmission

Myelin Sheaths in the PNS

• Schwann cells wraps many times around the axon

• Myelin sheath—concentric layers of Schwann cell membrane

• Neurilemma—peripheral bulge of Schwann cell cytoplasm

Myelin Sheaths in the PNS

• Nodes of Ranvier

• Myelin sheath gaps between adjacent Schwann cells

• Sites where axon collaterals can emerge

Figure 11.5a

(a) Myelination of a nervefiber (axon)

Schwann cellcytoplasm

Axon

Neurilemma

Myelin sheath

Schwann cellnucleus

Schwann cellplasma membrane

1

2

3

A Schwann cellenvelopes an axon.

The Schwann cell thenrotates around the axon, wrapping its plasma membrane loosely around it in successive layers.

The Schwann cellcytoplasm is forced from between the membranes. The tight membrane wrappings surrounding the axon form the myelin sheath.

Unmyelinated Axons

• Thin nerve fibers are unmyelinated

• One Schwann cell may incompletely enclose 15 or more unmyelinated axons

Myelin Sheaths in the CNS

• Formed by processes of oligodendrocytes, not the whole cells

• Nodes of Ranvier are present

• No neurilemma

• Thinnest fibers are unmyelinated

Figure 11.3d

(d) Oligodendrocytes have processes that formmyelin sheaths around CNS nerve fibers.

Nervefibers

Myelin sheath

Process ofoligodendrocyte

White Matter and Gray Matter

•White matter

• Dense collections of myelinated fibers

• Gray matter

• Mostly neuron cell bodies and unmyelinated fibers

Structural Classification of Neurons

• Three types:

1. Multipolar—1 axon and several dendrites

• Most abundant

• Motor neurons and interneurons

2. Bipolar—1 axon and 1 dendrite

• Rare, e.g., retinal neurons

Structural Classification of Neurons

3. Unipolar (pseudounipolar)—single, short process that has two branches:

• Peripheral process—more distal branch, often associated with a sensory receptor

• Central process—branch entering the CNS

Table 11.1 (1 of 3)

Table 11.1 (2 of 3)

Functional Classification of Neurons

• Three types:

1. Sensory (afferent)

• Transmit impulses from sensory receptors toward the CNS

2. Motor (efferent)

• Carry impulses from the CNS to effectors

Functional Classification of Neurons

3. Interneurons (association neurons)

• Shuttle signals through CNS pathways; most are entirely within the CNS

Table 11.1 (3 of 3)

Neuron Function

• Neurons are highly irritable

• Respond to adequate stimulus by generating an action potential (nerve impulse)

• Impulse is always the same regardless of stimulus

Principles of Electricity

• Opposite charges attract each other

• Energy is required to separate opposite charges across a membrane

• Energy is liberated when the charges move toward one another

• If opposite charges are separated, the system has potential energy

Definitions

• Voltage (V): measure of potential energy generated by separated charge

• Potential difference: voltage measured between two points

• Current (I): the flow of electrical charge (ions) between two points

Definitions

• Resistance (R): hindrance to charge flow (provided by the plasma membrane)

• Insulator: substance with high electrical resistance

• Conductor: substance with low electrical resistance

Role of Membrane Ion Channels

• Proteins serve as membrane ion channels

• Two main types of ion channels

1. Leakage (nongated) channels—always open

Role of Membrane Ion Channels

2. Gated channels (three types):

• Chemically gated (ligand-gated) channels—open with binding of a specific neurotransmitter

• Voltage-gated channels—open and close in response to changes in membrane potential

• Mechanically gated channels—open and close in response to physical deformation of receptors

Figure 11.6

(b) Voltage-gated ion channels open and close in responseto changes in membrane voltage.

Na+

Na+

Closed Open

Receptor

(a) Chemically (ligand) gated ion channels open when theappropriate neurotransmitter binds to the receptor,allowing (in this case) simultaneous movement of Na+ and K+.

Na+

K+

K+

Na+

Neurotransmitter chemicalattached to receptor

Chemicalbinds

Closed Open

Membranevoltagechanges

Gated Channels

•When gated channels are open:

• Ions diffuse quickly across the membrane along their electrochemical gradients

• Along chemical concentration gradients from higher concentration to lower concentration

• Along electrical gradients toward opposite electrical charge

• Ion flow creates an electrical current and voltage changes across the membrane

Resting Membrane Potential (Vr)

• Potential difference across the membrane of a resting cell

• Approximately –70 mV in neurons (cytoplasmic side of membrane is negatively charged relative to outside)

• Generated by:

• Differences in ionic makeup of ICF and ECF

• Differential permeability of the plasma membrane

Figure 11.7

Voltmeter

Microelectrodeinside cell

Plasmamembrane

Ground electrodeoutside cell

Neuron

Axon

Resting Membrane Potential

• Differences in ionic makeup

• ICF has lower concentration of Na+ and Cl– than ECF

• ICF has higher concentration of K+ and negatively charged proteins (A–) than ECF

Resting Membrane Potential

• Differential permeability of membrane

• Impermeable to A–

• Slightly permeable to Na+ (through leakage channels)

• 75 times more permeable to K+ (more leakage channels)

• Freely permeable to Cl–

Resting Membrane Potential

• Negative interior of the cell is due to much greater diffusion of K+ out of the cell than Na+ diffusion into the cell

• Sodium-potassium pump stabilizes the resting membrane potential by maintaining the concentration gradients for Na+ and K+

Figure 11.8

Finally, let’s add a pump to compensate for leaking ions.Na+-K+ ATPases (pumps) maintain the concentration gradients, resulting in the resting membrane potential.

Suppose a cell has only K+ channels...K+ loss through abundant leakagechannels establishes a negativemembrane potential.

Now, let’s add some Na+ channels to our cell...Na+ entry through leakage channels reducesthe negative membrane potential slightly.

The permeabilities of Na+ and K+ across the membrane are different.

The concentrations of Na+ and K+ on each side of the membrane are different.

Na+

(140 mM )K+

(5 mM )

K+ leakage channels

Cell interior–90 mV

Cell interior–70 mV

Cell interior–70 mV

K+

Na+

Na+-K+ pump

K+

K+K+

K+

Na+

K+

K+K

Na+

K+K+ Na+

K+K+

Outside cell

Inside cellNa+-K+ ATPases (pumps) maintain the concentration gradients of Na+ and K+

across the membrane.

The Na+ concentration is higher outside the cell.

The K+ concentration is higher inside the cell.

K+

(140 mM )Na+

(15 mM )

Membrane Potentials That Act as Signals

• Membrane potential changes when:

• Concentrations of ions across the membrane change

• Permeability of membrane to ions changes

• Changes in membrane potential are signals used to receive, integrate and send information

Membrane Potentials That Act as Signals

• Two types of signals

• Graded potentials

• Incoming short-distance signals

• Action potentials

• Long-distance signals of axons

Changes in Membrane Potential

• Depolarization

• A reduction in membrane potential (toward zero)

• Inside of the membrane becomes less negative than the resting potential

• Increases the probability of producing a nerve impulse

Figure 11.9a

Depolarizing stimulus

Time (ms)

Insidepositive

Insidenegative

Restingpotential

Depolarization

(a) Depolarization: The membrane potentialmoves toward 0 mV, the inside becoming less negative (more positive).

Changes in Membrane Potential

• Hyperpolarization

• An increase in membrane potential (away from zero)

• Inside of the membrane becomes more negative than the resting potential

• Reduces the probability of producing a nerve impulse

Figure 11.9b

Hyperpolarizing stimulus

Time (ms)

Restingpotential

Hyper-polarization

(b) Hyperpolarization: The membranepotential increases, the inside becomingmore negative.

Graded Potentials

• Short-lived, localized changes in membrane potential

• Depolarizations or hyperpolarizations

• Graded potential spreads as local currents change the membrane potential of adjacent regions

Figure 11.10a

Depolarized region

Stimulus

Plasmamembrane

(a) Depolarization: A small patch of the membrane (red area) has become depolarized.

Figure 11.10b

(b) Spread of depolarization: The local currents (black arrows) that are created depolarize adjacent membrane areas and allow the wave of depolarization to spread.

Graded Potentials

• Occur when a stimulus causes gated ion channels to open

• E.g., receptor potentials, generator potentials, postsynaptic potentials

• Magnitude varies directly (graded) with stimulus strength

• Decrease in magnitude with distance as ions flow and diffuse through leakage channels

• Short-distance signals

Figure 11.10c

Distance (a few mm)

–70Resting potential

Active area(site of initialdepolarization)

(c) Decay of membrane potential with distance: Because current is lost through the “leaky” plasma membrane, the voltage declines with distance from the stimulus (the voltage is decremental ). Consequently, graded potentials are short-distance signals.

Mem

bra

ne p

ote

nti

al (m

V)

Action Potential (AP)

• Brief reversal of membrane potential with a total amplitude of ~100 mV

• Occurs in muscle cells and axons of neurons

• Does not decrease in magnitude over distance

• Principal means of long-distance neural communication

Actionpotential

1 2 3

4

Resting state Depolarization Repolarization

Hyperpolarization

The big picture

1 1

2

3

4

Time (ms)

ThresholdMem

bra

ne p

ote

nti

al (m

V)

Figure 11.11 (1 of 5)

Generation of an Action Potential

• Resting state

• Only leakage channels for Na+ and K+ are open

• All gated Na+ and K+ channels are closed

Properties of Gated Channels

• Properties of gated channels

• Each Na+ channel has two voltage-sensitive gates

• Activation gates

• Closed at rest; open with depolarization

• Inactivation gates

• Open at rest; block channel once it is open

Properties of Gated Channels

• Each K+ channel has one voltage-sensitive gate

• Closed at rest

• Opens slowly with depolarization

Depolarizing Phase

• Depolarizing local currents open voltage-gated Na+ channels

• Na+ influx causes more depolarization

• At threshold (–55 to –50 mV) positive feedback leads to opening of all Na+ channels, and a reversal of membrane polarity to +30mV (spike of action potential)

Repolarizing Phase

• Repolarizing phase

• Na+ channel slow inactivation gates close

• Membrane permeability to Na+ declines to resting levels

• Slow voltage-sensitive K+ gates open

• K+ exits the cell and internal negativity is restored

Hyperpolarization

• Hyperpolarization

• Some K+ channels remain open, allowing excessive K+ efflux

• This causes after-hyperpolarization of the membrane (undershoot)

Actionpotential

Time (ms)

1 1

2

3

4

Na+ permeability

K+ permeability

The AP is caused by permeability changes inthe plasma membrane

Mem

bra

ne p

ote

nti

al (m

V)

Rela

tive m

em

bra

ne p

erm

eab

ility

Figure 11.11 (2 of 5)

Role of the Sodium-Potassium Pump

• Repolarization

• Restores the resting electrical conditions of the neuron

• Does not restore the resting ionic conditions

• Ionic redistribution back to resting conditions is restored by the thousands of sodium-potassium pumps

Propagation of an Action Potential

• Na+ influx causes a patch of the axonal membrane to depolarize

• Local currents occur

• Na+ channels toward the point of origin are inactivated and not affected by the local currents

Propagation of an Action Potential

• Local currents affect adjacent areas in the forward direction

• Depolarization opens voltage-gated channels and triggers an AP

• Repolarization wave follows the depolarization wave

• (Fig. 11.12 shows the propagation process in unmyelinated axons.)

Figure 11.12a

Voltageat 0 ms

Recordingelectrode

(a) Time = 0 ms. Action potential has not yet reached the recording electrode.

Resting potential

Peak of action potential

Hyperpolarization

Figure 11.12b

Voltageat 2 ms

(b) Time = 2 ms. Action potential peak is at the recording electrode.

Figure 11.12c

Voltageat 4 ms

(c) Time = 4 ms. Action potential peak is past the recording electrode. Membrane at the recording electrode is still hyperpolarized.

Threshold

• At threshold:

• Membrane is depolarized by 15 to 20 mV

• Na+ permeability increases

• Na influx exceeds K+ efflux

• The positive feedback cycle begins

Threshold

• Subthreshold stimulus—weak local depolarization that does not reach threshold

• Threshold stimulus—strong enough to push the membrane potential toward and beyond threshold

• AP is an all-or-none phenomenon—action potentials either happen completely, or not at all

Coding for Stimulus Intensity

• All action potentials are alike and are independent of stimulus intensity

• How does the CNS tell the difference between a weak stimulus and a strong one?

• Strong stimuli can generate action potentials more often than weaker stimuli

• The CNS determines stimulus intensity by the frequency of impulses

Figure 11.13

Threshold

Actionpotentials

Stimulus

Time (ms)

Absolute Refractory Period

• Time from the opening of the Na+ channels until the resetting of the channels

• Ensures that each AP is an all-or-none event

• Enforces one-way transmission of nerve impulses

Figure 11.14

Stimulus

Absolute refractoryperiod

Relative refractoryperiod

Time (ms)

Depolarization(Na+ enters)

Repolarization(K+ leaves)

After-hyperpolarization

Relative Refractory Period

• Follows the absolute refractory period

• Most Na+ channels have returned to their resting state

• Some K+ channels are still open

• Repolarization is occurring

• Threshold for AP generation is elevated

• Exceptionally strong stimulus may generate an AP

Conduction Velocity

• Conduction velocities of neurons vary widely

• Effect of axon diameter

• Larger diameter fibers have less resistance to local current flow and have faster impulse conduction

• Effect of myelination

• Continuous conduction in unmyelinated axons is slower than saltatory conduction in myelinated axons

Conduction Velocity

• Effects of myelination

• Myelin sheaths insulate and prevent leakage of charge

• Saltatory conduction in myelinated axons is about 30 times faster

• Voltage-gated Na+ channels are located at the nodes

• APs appear to jump rapidly from node to node

Figure 11.15

Size of voltage

Voltage-gatedion channel

Stimulus

Myelinsheath

Stimulus

Stimulus

Node of Ranvier

Myelin sheath

(a) In a bare plasma membrane (without voltage-gatedchannels), as on a dendrite, voltage decays becausecurrent leaks across the membrane.

(b) In an unmyelinated axon, voltage-gated Na+ and K+

channels regenerate the action potential at each pointalong the axon, so voltage does not decay. Conduction is slow because movements of ions and of the gatesof channel proteins take time and must occur beforevoltage regeneration occurs.

(c) In a myelinated axon, myelin keeps current in axons(voltage doesn’t decay much). APs are generated onlyin the nodes of Ranvier and appear to jump rapidlyfrom node to node.

1 mm

Multiple Sclerosis (MS)

• An autoimmune disease that mainly affects young adults

• Symptoms: visual disturbances, weakness, loss of muscular control, speech disturbances, and urinary incontinence

• Myelin sheaths in the CNS become nonfunctional scleroses

• Shunting and short-circuiting of nerve impulses occurs

• Impulse conduction slows and eventually ceases

Multiple Sclerosis: Treatment

• Some immune system–modifying drugs, including interferons and Copazone:

• Hold symptoms at bay

• Reduce complications

• Reduce disability

Nerve Fiber Classification

• Nerve fibers are classified according to:

• Diameter

• Degree of myelination

• Speed of conduction

Nerve Fiber Classification

• Group A fibers

• Large diameter, myelinated somatic sensory and motor fibers

• Group B fibers

• Intermediate diameter, lightly myelinated ANS fibers

• Group C fibers

• Smallest diameter, unmyelinated ANS fibers