The master controlling and communicating system of the body

Functionso Sensory input – monitoring stimuli o Integration – interpretation of sensory inputo Motor output – response to stimuli

Figure 11.1

Central nervous system (CNS) o Brain and spinal cordo Integration and command center

Peripheral nervous system (PNS)o Paired spinal and cranial nerveso Carries messages to and from the spinal cord and brain

Sensory (afferent) divisiono Sensory afferent fibers – carry impulses from skin,

skeletal muscles, and joints to the braino Visceral afferent fibers – transmit impulses from visceral

organs to the brain Motor (efferent) division

o Transmits impulses from the CNS to effector organs

Somatic nervous systemo Conscious control of skeletal muscles

Autonomic nervous system (ANS)o Regulates smooth muscle, cardiac muscle, and glandso Divisions – sympathetic and parasympathetic

The two principal cell types of the nervous system are:o Neurons – excitable cells that transmit electrical signalso Supporting cells – cells that surround and wrap neurons

The supporting cells (neuroglia or glial cells):o Provide a supportive scaffolding for neuronso Segregate and insulate neuronso Guide young neurons to the proper connections o Promote health and growth

Most abundant, versatile, and highly branched glial cells

They cling to neurons and their synaptic endings, and cover capillaries

Functionally, they:o Support and brace neuronso Anchor neurons to their nutrient supplieso Guide migration of young neuronso Control the chemical environment

Microglia – small, oval cells with spiny processeso Phagocytes that monitor the health of neurons

Ependymal cells – range in shape from squamous to columnaro They line the central cavities of the brain and spinal

column

Microglia Ependymal Cells

Oligodendrocytes – branched cells that wrap CNS nerve fibers with myelin

Schwann cells (neurolemmocytes) – surround fibers of the PNS with myelin

Satellite cells surround neuron cell bodies with ganglia

Oligodendrocytes Schwann Cells Satellite Cells

Structural units of the nervous systemo Composed of a body, axon, and dendriteso Long-lived, amitotic, and have a high metabolic rate

Their plasma membrane function in:o Electrical signaling o Cell-to-cell signaling during development

Contains the nucleus and a nucleolus Is the major biosynthetic center Is the focal point for the outgrowth of neuronal

processes Has no centrioles (hence its amitotic nature) Has well-developed Nissl bodies (rough ER) Contains an axon hillock – cone-shaped area from

which axons arise

Armlike extensions from the soma Called tracts in the CNS and nerves in the PNS There are two types: axons and dendrites

Short, tapering, and diffusely branched processes They are the receptive, or input, regions of the

neuron Electrical signals are conveyed as graded

potentials (not action potentials)

Slender processes of uniform diameter arising from the hillock

Long axons are called nerve fibers Usually there is only one unbranched axon per

neuron Rare branches, if present, are called axon

collaterals Axonal terminal – branched terminus of an axon

Generate and transmit action potentials Secrete neurotransmitters from the axonal

terminals Movement along axons occurs in two ways

o Anterograde — toward axonal terminalo Retrograde — away from axonal terminal

Whitish, fatty (protein-lipoid), segmented sheath around most long axons

It functions to:o Protect the axono Electrically insulate fibers from one anothero Increase the speed of nerve impulse transmission

Formed by Schwann cells in the PNS A Schwann cell:

o Envelopes an axon in a trougho Encloses the axon with its plasma membraneo Has concentric layers of membrane that make up the

myelin sheath Neurilemma – remaining visible nucleus and

cytoplasm of a Schwann cell

Figure 11.5a–c

Gaps in the myelin sheath between adjacent Schwann cells

They are the sites where axon collaterals can emerge

A Schwann cell surrounds nerve fibers but coiling does not take place

Schwann cells partially enclose 15 or more axons

Both myelinated and unmyelinated fibers are present

Myelin sheaths are formed by oligodendrocytes Nodes of Ranvier are widely spaced There is no neurilemma

White matter – dense collections of myelinated fibers

Gray matter – mostly soma and unmyelinated fibers

Structural: o Multipolar — three or more processeso Bipolar — two processes (axon and dendrite)o Unipolar — single, short process

Functional: o Sensory (afferent) — transmit impulses toward the CNSo Motor (efferent) — carry impulses away from the CNSo Interneurons (association neurons) — shuttle signals

through CNS pathways

Table 11.1.1

Table 11.1.2

Table 11.1.3

Neurons are highly irritable Action potentials, or nerve impulses, are:

o Electrical impulses carried along the length of axonso Always the same regardless of stimuluso The underlying functional feature of the nervous system

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

Potential difference – voltage measured between two points

Current (I) – the flow of electrical charge between two points

Resistance (R) – hindrance to charge flow Insulator – substance with high electrical

resistance Conductor – substance with low electrical

resistance

Reflects the flow of ions rather than electrons There is a potential on either side of membranes

when:o The number of ions is different across the membraneo The membrane provides a resistance to ion flow

Types of plasma membrane ion channels:o Passive, or leakage, channels – always openo Chemically gated channels – open with binding of a

specific neurotransmittero Voltage-gated channels – open and close in response to

membrane potentialo Mechanically gated channels – open and close in

response to physical deformation of receptors

Example: Na+-K+ gated channel Closed when a neurotransmitter is not bound to

the extracellular receptoro Na+ cannot enter the cell and K+ cannot exit the cell

Open when a neurotransmitter is attached to the receptoro Na+ enters the cell and K+ exits the cell

Example: Na+ channel Closed when the intracellular environment is

negative o Na+ cannot enter the cell

Open when the intracellular environment is positive o Na+ can enter the cell

When gated channels are open: o Ions move quickly across the membrane o Movement is along their electrochemical gradientso An electrical current is createdo Voltage changes across the membrane

Ions flow along their chemical gradient when they move from an area of high concentration to an area of low concentration

Ions flow along their electrical gradient when they move toward an area of opposite charge

Electrochemical gradient – the electrical and chemical gradients taken together

The potential difference (–70 mV) across the membrane of a resting neuron

It is generated by different concentrations of Na+, K+, Cl, and protein anions (A)

Ionic differences are the consequence of:o Differential permeability of the neurilemma to Na+ and

K+

o Operation of the sodium-potassium pump

Figure 11.8

Used to integrate, send, and receive information Membrane potential changes are produced by:

o Changes in membrane permeability to ionso Alterations of ion concentrations across the membrane

Types of signals – graded potentials and action potentials

Changes are caused by three eventso Depolarization – the inside of the membrane becomes

less negative o Repolarization – the membrane returns to its resting

membrane potentialo Hyperpolarization – the inside of the membrane

becomes more negative than the resting potential

Short-lived, local changes in membrane potential Decrease in intensity with distance Magnitude varies directly with the strength of the

stimulus Sufficiently strong graded potentials can initiate

action potentials

Figure 11.10

Voltage changes are decremental Current is quickly dissipated due to the leaky

plasma membrane Only travel over short distances

A brief reversal of membrane potential with a total amplitude of 100 mV

Action potentials are only generated by muscle cells and neurons

They do not decrease in strength over distance They are the principal means of neural

communication An action potential in the axon of a neuron is a

nerve impulse

Na+ and K+ channels are closed Leakage accounts for small movements of

Na+ and K+

Each Na+ channel has two voltage-regulated gates o Activation gates –

closed in the resting state

o Inactivation gates – open in the resting state

Figure 11.12.1

Na+ permeability increases; membrane potential reverses

Na+ gates are opened; K+ gates are closed Threshold – a critical level of depolarization

(-55 to -50 mV) At threshold,

depolarization becomes self-generating

Figure 11.12.2

Sodium inactivation gates close Membrane permeability to Na+ declines to resting

levels As sodium gates close, voltage-sensitive K+ gates

open K+ exits the cell and

internal negativity of the resting neuron is restored

Figure 11.12.3

Potassium gates remain open, causing an excessive efflux of K+

This efflux causes hyperpolarization of the membrane (undershoot)

The neuron is insensitive to stimulus and depolarization during this time

Figure 11.12.4

Repolarization o Restores the resting electrical conditions of the neurono Does not restore the resting ionic conditions

Ionic redistribution back to resting conditions is restored by the sodium-potassium pump

1 – resting state 2 – depolarization

phase 3 – repolarization

phase 4 –

hyperpolarization

Figure 11.12

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

Positive ions in the axoplasm move toward the polarized (negative) portion of the membrane

Sodium gates are shown as closing, open, or closed

Figure 11.13a

Ions of the extracellular fluid move toward the area of greatest negative charge

A current is created that depolarizes the adjacent membrane in a forward direction

The impulse propagates away from its point of origin

Figure 11.13b

The action potential moves away from the stimulus

Where sodium gates are closing, potassium gates are open and create a current flow

Figure 11.13c

Threshold – membrane is depolarized by 15 to 20 mV

Established by the total amount of current flowing through the membrane

Weak (subthreshold) stimuli are not relayed into action potentials

Strong (threshold) stimuli are relayed into action potentials

All-or-none phenomenon – action potentials either happen completely, or not at all

All action potentials are alike and are independent of stimulus intensity

Strong stimuli can generate an action potential more often than weaker stimuli

The CNS determines stimulus intensity by the frequency of impulse transmission

Figure 11.14

Time from the opening of the Na+ activation gates until the closing of inactivation gates

The absolute refractory period:o Prevents the neuron from generating an action potentialo Ensures that each action potential is separateo Enforces one-way transmission of nerve impulses

Figure 11.15

The interval following the absolute refractory period when:o Sodium gates are closedo Potassium gates are openo Repolarization is occurring

The threshold level is elevated, allowing strong stimuli to increase the frequency of action potential events

Conduction velocities vary widely among neurons Rate of impulse propagation is determined by:

o Axon diameter – the larger the diameter, the faster the impulse

o Presence of a myelin sheath – myelination dramatically increases impulse speed

Current passes through a myelinated axon only at the nodes of Ranvier

Voltage-gated Na+ channels are concentrated at these nodes

Action potentials are triggered only at the nodes and jump from one node to the next

Much faster than conduction along unmyelinated axons

Figure 11.16

An autoimmune disease that mainly affects young adults

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

Nerve fibers are severed and myelin sheaths in the CNS become nonfunctional scleroses

Shunting and short-circuiting of nerve impulses occurs

The advent of disease-modifying drugs including interferon beta-1a and -1b, Avonex, Betaseran, and Copazone:o Hold symptoms at bayo Reduce complicationso Reduce disability

Nerve fibers are classified according to:o Diametero Degree of myelinationo Speed of conduction

A junction that mediates information transfer from one neuron:o To another neurono To an effector cell

Presynaptic neuron – conducts impulses toward the synapse

Postsynaptic neuron – transmits impulses away from the synapse

Axodendritic – synapses between the axon of one neuron and the dendrite of another

Axosomatic – synapses between the axon of one neuron and the soma of another

Other types of synapses include:o Axoaxonic (axon to axon)o Dendrodendritic (dendrite to dendrite)o Dendrosomatic (dendrites to soma)

Electrical synapses:o Are less common than chemical synapseso Correspond to gap junctions found in other cell

typeso Are important in the CNS in:

• Arousal from sleep• Mental attention• Emotions and memory• Ion and water homeostasis

Specialized for the release and reception of neurotransmitters

Typically composed of two parts: o Axonal terminal of the presynaptic neuron, which

contains synaptic vesicles o Receptor region on the dendrite(s) or soma of the

postsynaptic neuron

Fluid-filled space separating the presynaptic and postsynaptic neurons

Prevents nerve impulses from directly passing from one neuron to the next

Transmission across the synaptic cleft: o Is a chemical event (as opposed to an electrical one)o Ensures unidirectional communication between neurons

Nerve impulses reach the axonal terminal of the presynaptic neuron and open Ca2+ channels

Neurotransmitter is released into the synaptic cleft via exocytosis in response to synaptotagmin

Neurotransmitter crosses the synaptic cleft and binds to receptors on the postsynaptic neuron

Postsynaptic membrane permeability changes, causing an excitatory or inhibitory effect

Synaptic vesiclescontaining neurotransmitter molecules

Axon of presynapticneuron

Synapticcleft

Ion channel(closed)

Ion channel (open)

Axon terminal of presynaptic neuron

PostsynapticmembraneMitochondrion

Ion channel closed

Ion channel open

Neurotransmitter

Receptor

Postsynapticmembrane

Degradedneurotransmitter

Na+Ca2+

1

2

34

5

Action

potential

Figure 11.18

Neurotransmitter bound to a postsynaptic neuron: o Produces a continuous postsynaptic effecto Blocks reception of additional “messages” o Must be removed from its receptor

Removal of neurotransmitters occurs when they:o Are degraded by enzymeso Are reabsorbed by astrocytes or the presynaptic

terminals o Diffuse from the synaptic cleft

Neurotransmitter must be released, diffuse across the synapse, and bind to receptors

Synaptic delay – time needed to do this (0.3-5.0 ms)

Synaptic delay is the rate-limiting step of neural transmission

Neurotransmitter receptors mediate changes in membrane potential according to:o The amount of neurotransmitter releasedo The amount of time the neurotransmitter is bound to

receptors The two types of postsynaptic potentials are:

o EPSP – excitatory postsynaptic potentials o IPSP – inhibitory postsynaptic potentials

EPSPs are graded potentials that can initiate an action potential in an axono Use only chemically gated channelso Na+ and K+ flow in opposite directions at the same time

Postsynaptic membranes do not generate action potentials

Figure 11.19a

Neurotransmitter binding to a receptor at inhibitory synapses: o Causes the membrane to become more permeable to

potassium and chloride ions o Leaves the charge on the inner surface negativeo Reduces the postsynaptic neuron’s ability to produce an

action potential

Figure 11.19b

A single EPSP cannot induce an action potential EPSPs must summate temporally or spatially to

induce an action potential Temporal summation – presynaptic neurons

transmit impulses in rapid-fire order

Spatial summation – postsynaptic neuron is stimulated by a large number of terminals at the same time

IPSPs can also summate with EPSPs, canceling each other out

Figure 11.20

Chemicals used for neuronal communication with the body and the brain

50 different neurotransmitters have been identified

Classified chemically and functionally

Acetylcholine (ACh) Biogenic amines Amino acids Peptides Novel messengers: ATP and dissolved gases NO

and CO

First neurotransmitter identified, and best understood

Released at the neuromuscular junction Synthesized and enclosed in synaptic vesicles

Degraded by the enzyme acetylcholinesterase (AChE)

Released by:o All neurons that stimulate skeletal muscleo Some neurons in the autonomic nervous system

Include:o Catecholamines – dopamine, norepinephrine (NE), and

epinephrineo Indolamines – serotonin and histamine

Broadly distributed in the brain Play roles in emotional behaviors and our

biological clock

Enzymes present in the cell determine length of biosynthetic pathway

Norepinephrine and dopamine are synthesized in axonal terminals

Epinephrine is released by the adrenal medulla

Figure 11.21

Include:o GABA – Gamma ()-aminobutyric acid o Glycineo Aspartateo Glutamate

Found only in the CNS

Include:o Substance P – mediator of pain signalso Beta endorphin, dynorphin, and enkephalins

Act as natural opiates; reduce pain perception Bind to the same receptors as opiates and

morphine Gut-brain peptides – somatostatin, and

cholecystokinin

ATPo Is found in both the CNS and PNSo Produces excitatory or inhibitory responses depending

on receptor typeo Induces Ca2+ wave propagation in astrocyteso Provokes pain sensation

Nitric oxide (NO) o Activates the intracellular receptor guanylyl cyclaseo Is involved in learning and memory

Carbon monoxide (CO) is a main regulator of cGMP in the brain

Two classifications: excitatory and inhibitoryo Excitatory neurotransmitters cause depolarizations

(e.g., glutamate)o Inhibitory neurotransmitters cause hyperpolarizations

(e.g., GABA and glycine)

Some neurotransmitters have both excitatory and inhibitory effects o Determined by the receptor type of the postsynaptic

neuron o Example: acetylcholine

• Excitatory at neuromuscular junctions with skeletal muscle• Inhibitory in cardiac muscle

Direct: neurotransmitters that open ion channelso Promote rapid responses o Examples: ACh and amino acids

Indirect: neurotransmitters that act through second messengerso Promote long-lasting effectso Examples: biogenic amines, peptides, and dissolved

gases

Composed of integral membrane protein- a protein permanently attached to the cell membrane

Mediate direct neurotransmitter action Action is immediate, brief, simple, and highly

localized Ligand binds the receptor, and ions enter the

cells Excitatory receptors depolarize membranes Inhibitory receptors hyperpolarize membranes

Figure 11.22a

Responses are indirect, slow, complex, prolonged, and often diffuse

These receptors are transmembrane protein complexes

Examples: muscarinic ACh receptors, neuropeptides, and those that bind biogenic amines

G protein-linked receptors activate intracellular second messengers including Ca2+, cGMP, diacylglycerol, as well as cAMP

Second messengers:o Open or close ion channelso Activate kinase enzymeso Phosphorylate channel proteins o Activate genes and induce protein synthesis

Functional groups of neurons that:o Integrate incoming informationo Forward the processed information to its appropriate

destination

Simple neuronal poolo Input fiber – presynaptic fibero Discharge zone – neurons most closely associated with

the incoming fibero Facilitated zone – neurons farther away from incoming

fiber

Figure 11.23

Divergent – one incoming fiber stimulates ever increasing number of fibers, often amplifying circuits

Figure 11.24a, b

Convergent – opposite of divergent circuits, resulting in either strong stimulation or inhibition

Figure 11.24c, d

Reverberating – chain of neurons containing collateral synapses with previous neurons in the chain

Figure 11.24e

Parallel after-discharge – incoming neurons stimulate several neurons in parallel arrays

Figure 11.24f

Serial Processingo Input travels along one pathway to a specific destinationo Works in an all-or-none mannero Example: spinal reflexes

Parallel Processingo Input travels along several pathwayso Pathways are integrated in different CNS systemso One stimulus promotes numerous responses

Example: a smell may remind one of the odor and associated experiences

The nervous system originates from the neural tube and neural crest

The neural tube becomes the CNS There is a three-phase process of differentiation:

o Proliferation of cells needed for developmento Migration – cells become amitotic and move externallyo Differentiation into neuroblasts

Guided by:o Scaffold laid down by older neuronso Orienting glial fiberso Release of nerve growth factor by astrocyteso Neurotropins released by other neuronso Repulsion guiding moleculeso Attractants released by target cells

N-CAM – nerve cell adhesion molecule Important in establishing neural pathways Without N-CAM, neural function is impaired Found in the membrane of the growth cone