NERVOUS NERVOUS SYSTEMSYSTEM

NERVOUS FUNCTIONSNERVOUS FUNCTIONS Body’s master controlling and communicating Body’s master controlling and communicating

systemsystem Three functionsThree functions

• Sensory inputSensory input Gathers information Gathers information

from sensory receptorsfrom sensory receptors

• IntegrationIntegration Processes and interprets Processes and interprets

sensory inputsensory input

• Motor outputMotor output Activates effector organs to cause a responseActivates effector organs to cause a response

Nervous System Nervous System OrganizationOrganization

ORGANIZATIONORGANIZATIONTwo Principal Parts of the SystemTwo Principal Parts of the System Central nervous system (CNS)Central nervous system (CNS)

• Brain and spinal cordBrain and spinal cord• Integrating and command centerIntegrating and command center

Interprets sensory inputInterprets sensory input Dictates motor responsesDictates motor responses

Peripheral nervous system (PNS)Peripheral nervous system (PNS)• Nerves extending from brain and spinal cordNerves extending from brain and spinal cord• Carry impulses to and from the CNSCarry impulses to and from the CNS

PERIPHERAL DIVISIONSPERIPHERAL DIVISIONSTwo Functional Subdivisions of the PNSTwo Functional Subdivisions of the PNS Sensory divisionSensory division

• “ “afferent division”afferent division”• Nerve fibers conveying impulses to the CNSNerve fibers conveying impulses to the CNS

Somatic afferent fibersSomatic afferent fibers convey impulses from the skin, convey impulses from the skin, muscles, and jointsmuscles, and joints

Visceral afferent fibersVisceral afferent fibers convey impulses from visceral convey impulses from visceral organsorgans

Motor divisionMotor division• , “efferent division”, “efferent division”• Nerve fibers conveying impulses from the CNSNerve fibers conveying impulses from the CNS

ORGANIZATIONORGANIZATION

HISTOLOGYHISTOLOGY Nervous system consists mainly of nervous Nervous system consists mainly of nervous

tissuetissue Highly cellularHighly cellular

• e.g., <20% extracellular space in CNSe.g., <20% extracellular space in CNS Two principal cell typesTwo principal cell types

• NeuronsNeurons Excitable nerve cells that transmit electrical signalsExcitable nerve cells that transmit electrical signals

• Supporting cellsSupporting cells Smaller cells surrounding and wrapping neuronsSmaller cells surrounding and wrapping neurons ““Neuroglia”Neuroglia”

NEUROGLIANEUROGLIA ““Nerve glue”Nerve glue” Six types of small cells associated with neuronsSix types of small cells associated with neurons

• 4 in CNS4 in CNS• 2 in PNS2 in PNS

Most have central cell body and branching Most have central cell body and branching processesprocesses

Several functionsSeveral functions• e.g., Supportive scaffolding for neuronse.g., Supportive scaffolding for neurons• e.g., Electrical isolation of neuronse.g., Electrical isolation of neurons• e.g., Neuron health and growthe.g., Neuron health and growth

CNS NEUROGLIACNS NEUROGLIA AstrocytesAstrocytes MicrogliaMicroglia Ependymal cellsEpendymal cells OligodendrocytesOligodendrocytes

CNS NEUROGLIACNS NEUROGLIAAstrocytesAstrocytes Most abundant and versatile glial cellsMost abundant and versatile glial cells Numerous processes support branching neuronsNumerous processes support branching neurons

• Anchor neurons to capillary blood supplyAnchor neurons to capillary blood supply Guide migration of young neuronsGuide migration of young neurons Facilitate nutrient delivery to neuronsFacilitate nutrient delivery to neurons

• (blood (blood glial cell glial cell neuron) neuron) Control chemical environment Control chemical environment

around neuronsaround neurons• Uptake of KUptake of K++, neurotransmitters, neurotransmitters

Communicate with astrocytes Communicate with astrocytes & neurons& neurons• Gap junctions Gap junctions

CNS NEUROGLIACNS NEUROGLIAMicrogliaMicroglia Small ovoid cellsSmall ovoid cells Relatively long “thorny” Relatively long “thorny”

processesprocesses• Processes touch nearby neuronsProcesses touch nearby neurons

Migrate toward injured neuronsMigrate toward injured neurons Transform into macrophageTransform into macrophage

• Phagocytize microorganisms, debrisPhagocytize microorganisms, debris

• (Cells of immune system cannot enter the CNS)(Cells of immune system cannot enter the CNS)

CNS NEUROGLIACNS NEUROGLIAEpendymal CellsEpendymal Cells Line central cavities of brain and spinal cordLine central cavities of brain and spinal cord

• Form permeable barrier between cerebrospinal fluid inside Form permeable barrier between cerebrospinal fluid inside these cavities and tissue fluid of CNS tissuethese cavities and tissue fluid of CNS tissue

Shapes range from squamous to columnarShapes range from squamous to columnar Many are ciliatedMany are ciliated

• Beating helps circulate cerebrospinal fluid cushioning brain Beating helps circulate cerebrospinal fluid cushioning brain and spinal cordand spinal cord

CNS NEUROGLIACNS NEUROGLIAOligodendrocytesOligodendrocytes Fewer processes than astrocytesFewer processes than astrocytes Wrap processes tightly around thicker neuron Wrap processes tightly around thicker neuron

fibers in CNSfibers in CNS• ““Myelin sheath”Myelin sheath”• Insulating coveringInsulating covering

PNS NEUROGLIAPNS NEUROGLIA Satellite cellsSatellite cells Schwann cellsSchwann cells

PNS NEUROGLIAPNS NEUROGLIASatellite cellsSatellite cells Surround neuron cell bodies within gangliaSurround neuron cell bodies within ganglia

• (A ganglion is a collection of nerve cell bodies (A ganglion is a collection of nerve cell bodies outside of the CNS)outside of the CNS)

Function poorly understoodFunction poorly understood

PNS NEUROGLIAPNS NEUROGLIASchwann cellsSchwann cells “ “Neurolemmocytes”Neurolemmocytes” Surround and form myelin sheaths around larger nerve Surround and form myelin sheaths around larger nerve

fibers of PNSfibers of PNS• Functionally similar to oligodendrocytesFunctionally similar to oligodendrocytes

Vital to regeneration of peripheral nerve fibersVital to regeneration of peripheral nerve fibers

NEURONSNEURONS Nerve cellsNerve cells Structural units of nervous systemStructural units of nervous system

• Billions are present in nervous systemBillions are present in nervous system Conduct messages throughout bodyConduct messages throughout body

• Nerve impulsesNerve impulses Extreme longevityExtreme longevity

• Can function optimally for entire lifetimeCan function optimally for entire lifetime AmitoticAmitotic

• Ability to divide is lost in mature cellsAbility to divide is lost in mature cells• Cannot be replaced if destroyedCannot be replaced if destroyed

Some (very few) exceptionsSome (very few) exceptions e.g., stem cells present in olfactory epithelium can produce new neuronse.g., stem cells present in olfactory epithelium can produce new neurons

• Stem cell research shows great promise in repairing damaged neuronsStem cell research shows great promise in repairing damaged neurons High metabolic rateHigh metabolic rate

• Require large amounts of oxygen and glucoseRequire large amounts of oxygen and glucose

NeurotrophinsNeurotrophins

Promote neuron growth.Promote neuron growth. Nerve growth factors include:Nerve growth factors include:

• Nerve growth factor (NGF), brain-derived neurotrophic factor Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), (BDNF), glial-derived neurotrophic factor (GDNF), neurotrophin-3, and neurotrophin-4/5.neurotrophin-3, and neurotrophin-4/5.

Fetus:Fetus:• Embryonic development of sensory neurons and sympathetic Embryonic development of sensory neurons and sympathetic

ganglia (NGF and neurotrophin-3).ganglia (NGF and neurotrophin-3). Adult:Adult:

• Maintenance of sympathetic ganglia (NGF).Maintenance of sympathetic ganglia (NGF).• Mature sensory neurons need for regeneration.Mature sensory neurons need for regeneration.• Required to maintain spinal neurons (GDNF).Required to maintain spinal neurons (GDNF).• Sustain neurons that use dopamine (GDNF).Sustain neurons that use dopamine (GDNF).

Myelin-associated inhibitory proteins:Myelin-associated inhibitory proteins:• Inhibit axon regeneration.Inhibit axon regeneration.

NeuronsNeurons

Axon of anotherneuron

Axon of anotherneuron

Cell BodyCell BodyDendritesDendrites

AxonAxon

MyelinSheathMyelinSheath

Dendrites of another neuron

Dendrites of another neuron

NEURONSNEURONS Generally large, complex cellsGenerally large, complex cells Structures vary, but all neurons have the same basic Structures vary, but all neurons have the same basic

structurestructure• Cell bodyCell body

• Slender processes Slender processes extending from cell extending from cell bodybody

• Plasma membrane Plasma membrane is site of signalingis site of signaling

NEURON CELL BODYNEURON CELL BODY Most neuron cell bodies are located in the CNSMost neuron cell bodies are located in the CNS

• Protected by bones of skull or vertebral columnProtected by bones of skull or vertebral column Clusters of cell bodies in the CNS are termed Clusters of cell bodies in the CNS are termed

“nuclei”“nuclei” Clusters of cell Clusters of cell

bodies in the bodies in the PNS are PNS are termed termed “ganglia”“ganglia”

NEURON CELL BODYNEURON CELL BODY a.k.a., “perikaryon” or “soma”a.k.a., “perikaryon” or “soma” 5 – 140 5 – 140 m in diameterm in diameter Transparent spherical nucleusTransparent spherical nucleus

• Contains Contains conspicuous conspicuous nucleolusnucleolus

NEURON CELL BODYNEURON CELL BODY Major biosynthetic center of neuronMajor biosynthetic center of neuron Other usual organelles presentOther usual organelles present

• ER & ribosomes most active and best developed in bodyER & ribosomes most active and best developed in body What do they do?What do they do?

• Centrioles absentCentrioles absent What do centrioles What do centrioles

do?do?

• Sometimes contains Sometimes contains pigment inclusionspigment inclusions

NEURON CELL BODYNEURON CELL BODY Focal point for the outgrowth of neuron processes Focal point for the outgrowth of neuron processes

during embryonic developmentduring embryonic development• Some processes receive signalsSome processes receive signals

• Plasma membrane Plasma membrane generally also acts generally also acts as part of the as part of the receptive surfacereceptive surface

NEURON PROCESSESNEURON PROCESSES Extend from the neuron’s cell bodyExtend from the neuron’s cell body CNS contains both neuron cell bodies and their CNS contains both neuron cell bodies and their

processesprocesses• Bundles of CNS processes are termed “tracts”Bundles of CNS processes are termed “tracts”

PNS consists mainly of neuronal processesPNS consists mainly of neuronal processes• Bundles of PNS processes are termed “nerves”Bundles of PNS processes are termed “nerves”

Two types of neuron processesTwo types of neuron processes• DendritesDendrites• AxonsAxons

NEURON PROCESSESNEURON PROCESSESTypical DendriteTypical Dendrite Short, tapering, diffusely branching extensionsShort, tapering, diffusely branching extensions

• Generally hundreds clustering close to cell bodyGenerally hundreds clustering close to cell body• Most cell body organelles also present in dendritesMost cell body organelles also present in dendrites

Main receptive / input regionsMain receptive / input regions• Large surface area for Large surface area for

receiving signals from receiving signals from other neuronsother neurons

• Convey incoming messages Convey incoming messages toward cell bodytoward cell body

• Short-distance signals are Short-distance signals are “graded potentials”“graded potentials”

Not action potentialsNot action potentials

NEURON PROCESSESNEURON PROCESSESTypical AxonTypical Axon Single axon per neuronSingle axon per neuron ““Axon hillock” of cell body narrows to form a slender Axon hillock” of cell body narrows to form a slender

process of uniform diameterprocess of uniform diameter Sometimes very shortSometimes very short Sometimes very longSometimes very long

• e.g., axons controlling e.g., axons controlling big toe are 3 – 4 feet big toe are 3 – 4 feet longlong

NEURON PROCESSESNEURON PROCESSESTypical AxonTypical Axon Single axon may branch along lengthSingle axon may branch along length ““Axon collaterals” extend from neurons at ~ 90Axon collaterals” extend from neurons at ~ 90oo angles angles Usually branches Usually branches

profusely at endprofusely at end• 10,000 or more 10,000 or more

terminal branches terminal branches is commonis common

• Distal endings Distal endings termed “axonal termed “axonal terminals”terminals”

NEURON PROCESSESNEURON PROCESSESTypical AxonTypical Axon Conducting component of neuronConducting component of neuron Generates nerve impulsesGenerates nerve impulses

• Generated at axon hillock / axon junction in motor neuronsGenerated at axon hillock / axon junction in motor neurons

• ““Trigger zone”Trigger zone” Transmits nerve Transmits nerve

impulses away from impulses away from cell bodycell body• To axonal terminalsTo axonal terminals

NEURON PROCESSESNEURON PROCESSESTypical AxonTypical Axon Axonal terminals are Axonal terminals are secretory componentsecretory component of neuron of neuron Sequence of eventsSequence of events

• Signal reaches terminalsSignal reaches terminals

• Membranes of vesicles fuse with Membranes of vesicles fuse with plasma membraneplasma membrane

““Axolemma”Axolemma”

• Neurotransmitters releasedNeurotransmitters released

• Neurotransmitters interact Neurotransmitters interact with either other neurons with either other neurons or effector cellsor effector cells

Excite or inhibitExcite or inhibit

NEURON PROCESSESNEURON PROCESSESTypical AxonTypical Axon Contains most of the same organelles found in dendrites Contains most of the same organelles found in dendrites

and cell bodyand cell body• Lacks ER and Golgi apparatusLacks ER and Golgi apparatus

NEURON PROCESSESNEURON PROCESSESTypical AxonTypical Axon Rely on cell body for some moleculesRely on cell body for some molecules Rely on efficient transport mechanisms for deliveryRely on efficient transport mechanisms for delivery

• AnterogradeAnterograde movement toward axonal terminals movement toward axonal terminals e.g., Mitochondria, e.g., Mitochondria,

membrane components, membrane components, neurotransmitters or neurotransmitters or enzymes required for enzymes required for neurotransmitter neurotransmitter synthesis, etc.synthesis, etc.

• RetrogradeRetrograde movement movement toward cell bodytoward cell body

e.g., Organelles being e.g., Organelles being returned for recyclingreturned for recycling

NEURON PROCESSESNEURON PROCESSESTypical AxonTypical Axon Some viruses and bacterial toxins use retrograde Some viruses and bacterial toxins use retrograde

transport to reach the cell bodytransport to reach the cell body• e.g., poliovirus, rabies virus, herpes simplex viruses, tetanus e.g., poliovirus, rabies virus, herpes simplex viruses, tetanus

toxin, etc.toxin, etc. Such viruses can be Such viruses can be

used as vehicles for the used as vehicles for the therapeutic delivery of therapeutic delivery of engineered DNAengineered DNA• ““Gene therapy”Gene therapy”

MYELIN SHEATHMYELIN SHEATH Whitish, fatty covering of many nerve fibers Whitish, fatty covering of many nerve fibers

• Particularly those long are large in diameterParticularly those long are large in diameter Protects and electrically insulates fibersProtects and electrically insulates fibers Increases speed of nerve impulse transmissionIncreases speed of nerve impulse transmission

• Some axons and all dendrites are unmyelinatedSome axons and all dendrites are unmyelinated

MYELIN SHEATHMYELIN SHEATH In PNS, myelin sheaths formed by Schwann cellsIn PNS, myelin sheaths formed by Schwann cells

• Continually wrap around nerveContinually wrap around nerve

• Cytoplasm gradually squeezed from intracellular spaceCytoplasm gradually squeezed from intracellular space

• Result is many concentric layers of plasma membrane Result is many concentric layers of plasma membrane surrounding the axonsurrounding the axon

These plasma membranes contain little proteinThese plasma membranes contain little protein• Some proteins present interlock adjacent membranesSome proteins present interlock adjacent membranes

• Thickness depends on number of wrappingsThickness depends on number of wrappings Nucleus and most of Nucleus and most of

cytoplasm exist as a bulge cytoplasm exist as a bulge external to the myelin sheathexternal to the myelin sheath• ““Neurilemma”Neurilemma”

MYELIN SHEATHMYELIN SHEATH Adjacent Schwann cells on axon do not touch Adjacent Schwann cells on axon do not touch

each othereach other• Gaps in sheath occur at regular intervals Gaps in sheath occur at regular intervals

““Nodes of Ranvier”Nodes of Ranvier” a.k.a., “Neurofibril a.k.a., “Neurofibril

nodes”nodes”

• Axon collaterals Axon collaterals can emerge at can emerge at these nodesthese nodes

MYELIN SHEATHMYELIN SHEATH CNS contains both myelinated and CNS contains both myelinated and

unmyelinated axonsunmyelinated axons• Those long are large in diameter are typically Those long are large in diameter are typically

myelinatedmyelinated Oligodendrocytes, not Schwann cells, form CNS Oligodendrocytes, not Schwann cells, form CNS

myelin sheathsmyelin sheaths• Oligodendrocytes possess numerous processes that Oligodendrocytes possess numerous processes that

can coil around numerous (up to 60) axons at once can coil around numerous (up to 60) axons at once CNS myelin sheaths lack a neurilemmaCNS myelin sheaths lack a neurilemma

MYELIN SHEATHMYELIN SHEATH White matterWhite matter

• Regions of the brain and spinal cord containing Regions of the brain and spinal cord containing dense collections of myelinated fibersdense collections of myelinated fibers

Gray matterGray matter• Regions of the brain and spinal cord containing Regions of the brain and spinal cord containing

mostly nerve cell bodies and unmyelinated fibersmostly nerve cell bodies and unmyelinated fibers

NEURON CLASSIFICATIONNEURON CLASSIFICATION Structural classification based upon number of Structural classification based upon number of

processesprocesses• Multipolar neuronsMultipolar neurons• Bipolar neuronsBipolar neurons• Unipolar neuronsUnipolar neurons

Functional classification based upon direction Functional classification based upon direction nerve impulse travelsnerve impulse travels• Sensory (afferent) neuronsSensory (afferent) neurons• Motor (efferent) neuronsMotor (efferent) neurons• Interneurons (association neurons)Interneurons (association neurons)

NEURON CLASSIFICATIONNEURON CLASSIFICATIONStructural ClassificationStructural Classification Multipolar neuronsMultipolar neurons

• Three or more processesThree or more processes• Most common neuron Most common neuron

type in humanstype in humans (> 99% of neurons)(> 99% of neurons)

Bipolar neuronsBipolar neurons• Two processes – axon and Two processes – axon and

dendritedendrite• Found only in some Found only in some

special sense organs special sense organs e.g., retina of eyee.g., retina of eye

• Act as receptor cellsAct as receptor cells

Unipolar neuronsUnipolar neurons• Single short processSingle short process• ““Pseudounipolar neurons”Pseudounipolar neurons”

Originate as bipolar neuronsOriginate as bipolar neurons Two processes converge and Two processes converge and

fuse fuse

• Process divides into proximal Process divides into proximal and distal branchesand distal branches

Distal process often associated Distal process often associated with a sensory receptorwith a sensory receptor

• ““Peripheral process”Peripheral process” Central process enters CNSCentral process enters CNS

• Most are sensory neurons in Most are sensory neurons in PNSPNS

Classification of neurons Classification of neurons by shapeby shape

NEURON CLASSIFICATIONNEURON CLASSIFICATIONFunctional ClassificationFunctional Classification Sensory (afferent) neuronsSensory (afferent) neurons

• Transmit impulses Transmit impulses towardtoward CNS CNS From sensory receptors or internal From sensory receptors or internal

organsorgans

• Most are unipolarMost are unipolar• Cell bodies are located outside Cell bodies are located outside

CNSCNS Motor (efferent) neuronsMotor (efferent) neurons

• Carry impulses Carry impulses away fromaway from CNS CNS Toward effector organsToward effector organs

• MultipolarMultipolar• Cell bodies generally located in Cell bodies generally located in

the CNSthe CNS

Interneurons Interneurons • a.k.a., association a.k.a., association

neuronsneurons• Lie between motor and Lie between motor and

sensory neurons in sensory neurons in neural pathwaysneural pathways

• Shuttle signals through Shuttle signals through CNS pathways where CNS pathways where integration occursintegration occurs

• > 99% of neurons in > 99% of neurons in body body

• Most are multipolarMost are multipolar• Most are confined Most are confined

within the CNSwithin the CNS

NEUROPHYSIOLOGYNEUROPHYSIOLOGY Neurons are highly irritableNeurons are highly irritable

• Responsive to stimuliResponsive to stimuli Response to stimulus is action potentialResponse to stimulus is action potential

• Electrical impulse carried along length of axonElectrical impulse carried along length of axon• Always the same regardless of stimulusAlways the same regardless of stimulus• The underlying functional feature of the nervous The underlying functional feature of the nervous

systemsystem

ION CHANNELSION CHANNELSPlasma membranes contain various ion channelsPlasma membranes contain various ion channels Passive channels (leakage channels)Passive channels (leakage channels)

• Always openAlways open Active channels (gated channels)Active channels (gated channels)

• Ligand-gated channelsLigand-gated channels Open when specific chemical bindsOpen when specific chemical binds

• Voltage-gated channelsVoltage-gated channels Open and close in response to membrane potentialOpen and close in response to membrane potential

• Mechanically-gated channelsMechanically-gated channels Open in response to physical deformation of receptorOpen in response to physical deformation of receptor

• e.g., touch and pressure receptorse.g., touch and pressure receptors

MEMBRANE POTENTIALSMEMBRANE POTENTIALS A voltage exists across the plasma membraneA voltage exists across the plasma membrane

• Due to separation of oppositely charged ionsDue to separation of oppositely charged ions Potential difference in a resting membrane is Potential difference in a resting membrane is

termed its termed its “resting membrane potential”“resting membrane potential”• ~ -70 mV in a resting ~ -70 mV in a resting

neuronneuron• Membrane is Membrane is

“polarized”“polarized”

MEMBRANE POTENTIALSMEMBRANE POTENTIALS Neurons use changes in membrane potentials as Neurons use changes in membrane potentials as

signalssignals• Used to receive, integrate, and send signalsUsed to receive, integrate, and send signals

Changes in membrane potentials produced byChanges in membrane potentials produced by• Anything changing membrane permeability to ionsAnything changing membrane permeability to ions• Anything altering ion concentrationsAnything altering ion concentrations

Two types of signalsTwo types of signals• Graded potentialsGraded potentials

Short-distance signalsShort-distance signals

• Action potentialsAction potentials Long-distance signalsLong-distance signals

MEMBRANE POTENTIALSMEMBRANE POTENTIALSGraded PotentialsGraded Potentials Short-lived local changes in membrane potentialShort-lived local changes in membrane potential

• Either depolarizations or hyperpolarizationsEither depolarizations or hyperpolarizations Cause current flows that decrease in magnitude Cause current flows that decrease in magnitude

with distancewith distance Magnitude of potential dependent upon stimulus Magnitude of potential dependent upon stimulus

strengthstrength• Stronger stimulus Stronger stimulus larger voltage change larger voltage change• Larger voltage change Larger voltage change farther current flows farther current flows

MEMBRANE POTENTIALSMEMBRANE POTENTIALSGraded PotentialsGraded Potentials Triggered by change in neuron’s environmentTriggered by change in neuron’s environment

• Change causes gated ion channels to openChange causes gated ion channels to open Small area of neuron’s plasma membrane becomes Small area of neuron’s plasma membrane becomes

depolarized (by this stimulus)depolarized (by this stimulus) Current flows on both sides of the membraneCurrent flows on both sides of the membrane

• + moves toward – and + moves toward – and vise versavise versa

MEMBRANE POTENTIALSMEMBRANE POTENTIALSGraded PotentialsGraded Potentials Inside cell: + ions move away from depolarized areaInside cell: + ions move away from depolarized area Outside cell: + ions move toward depolarized areaOutside cell: + ions move toward depolarized area

• (+ and – ions switch places)(+ and – ions switch places) Membrane is leakyMembrane is leaky

• Most of the charge is quickly lost through membraneMost of the charge is quickly lost through membrane

• Current dies out after traveling a short distanceCurrent dies out after traveling a short distance

MEMBRANE POTENTIALSMEMBRANE POTENTIALSGraded PotentialsGraded Potentials Act as signals over very short distancesAct as signals over very short distances Important in initiating action potentialsImportant in initiating action potentials

MEMBRANE POTENTIALSMEMBRANE POTENTIALSAction PotentialsAction Potentials Principal means by which neurons communicatePrincipal means by which neurons communicate

• Brief reversal of membrane potentialBrief reversal of membrane potential Total amplitude of ~ 100 mV (-70 Total amplitude of ~ 100 mV (-70 +30) +30)

• Depolarization followed by repolarization, then brief Depolarization followed by repolarization, then brief period of hyperpolarizationperiod of hyperpolarization

• Time for entire event is only a few millisecondsTime for entire event is only a few milliseconds Events in generation and transmission of an Events in generation and transmission of an

action potential identical between neurons and action potential identical between neurons and skeletal muscle cellsskeletal muscle cells

ACTION POTENTIALSACTION POTENTIALS

ACTION POTENTIALSACTION POTENTIALS Not all local depolarizations produce action Not all local depolarizations produce action

potentialspotentials Depolarization must reach threshold valuesDepolarization must reach threshold values

• Brief, weak stimuli produce subthreshold Brief, weak stimuli produce subthreshold depolarizations that are not translated into nerve depolarizations that are not translated into nerve impulsesimpulses

• Stronger threshold stimuli produce depolarizing Stronger threshold stimuli produce depolarizing eventsevents

ACTION POTENTIALSACTION POTENTIALS Action potential is all-or-nothing phenomenonAction potential is all-or-nothing phenomenon

• Happens completely or doesn’t happenHappens completely or doesn’t happen Independent of stimulus strength once generatedIndependent of stimulus strength once generated

• Strong stimuli generate Strong stimuli generate moremore impulses of the impulses of the samesame strength per unit timestrength per unit time

• Intensity is determined by number of impulses per Intensity is determined by number of impulses per unit timeunit time

ACTION POTENTIALSACTION POTENTIALSRefractory PeriodsRefractory Periods Neuron cannot respond to a second stimulus Neuron cannot respond to a second stimulus

while the Nawhile the Na++ channels are still open from channels are still open from previous stimulusprevious stimulus• This period of time is termed the This period of time is termed the “absolute “absolute

refractory period”refractory period” ““Relative refractory period”Relative refractory period” follows the follows the

absolute refractory periodabsolute refractory period• Repolarization is occurringRepolarization is occurring• Threshold for impulse generation is elevatedThreshold for impulse generation is elevated

Only strong stimuli can generate impulsesOnly strong stimuli can generate impulses

ACTION POTENTIALSACTION POTENTIALSConduction VelocitiesConduction Velocities Conduction velocities of neurons vary widelyConduction velocities of neurons vary widely Rate of impulse propagation dependent uponRate of impulse propagation dependent upon

• Axon diameterAxon diameter Larger axons conduct impulses fasterLarger axons conduct impulses faster

• Degree of myelinationDegree of myelination Myelin sheath dramatically increases rate of propagationMyelin sheath dramatically increases rate of propagation

• Myelin acts as an insulator to prevent almost all leakage from Myelin acts as an insulator to prevent almost all leakage from axonaxon

ACTION POTENTIALSACTION POTENTIALSMultiple Sclerosis (MS)Multiple Sclerosis (MS) Autoimmune disease mainly affecting young Autoimmune disease mainly affecting young

adultsadults Myelin sheaths in CNS are gradually destroyedMyelin sheaths in CNS are gradually destroyed Interferes with impulse conductionInterferes with impulse conduction

• Visual disturbances, muscle control problems, Visual disturbances, muscle control problems, speech disturbances, etc.speech disturbances, etc.

Some modern treatments showing some promise Some modern treatments showing some promise in delaying problemsin delaying problems

NERVE FIBERSNERVE FIBERS Classified based onClassified based on

• DiameterDiameter• Degree of myelinationDegree of myelination• Conduction speedConduction speed

NERVE FIBER CLASSIFICATIONNERVE FIBER CLASSIFICATION Group A fibersGroup A fibers

• Largest diameterLargest diameter• Thick myelin sheathsThick myelin sheaths• Conduct impulses at high speeds (> 300 mph)Conduct impulses at high speeds (> 300 mph)• Mostly somatic sensory ad motor fibers serving skin, skeletal Mostly somatic sensory ad motor fibers serving skin, skeletal

muscles, and jointsmuscles, and joints Group B fibersGroup B fibers

• Intermediate diameterIntermediate diameter• Lightly myelinatedLightly myelinated• Transmit impulses at moderate speeds (40 mph)Transmit impulses at moderate speeds (40 mph)

Group C fibersGroup C fibers• Smallest diameterSmallest diameter• UnmyelinatedUnmyelinated• Transmit impulses comparatively slowly (2 mph or less)Transmit impulses comparatively slowly (2 mph or less)

Nerve Fiber Nerve Fiber ClassificationClassification

General classification scheme (Erlanger-Gasser):General classification scheme (Erlanger-Gasser):• A fibers: MyelinatedA fibers: Myelinated

Subtypes: Subtypes: some overlap in rangessome overlap in ranges Fastest conducting and largest diameter – Fastest conducting and largest diameter – m/sec, m/sec, ““A” often dropped: alpha motor neuronA” often dropped: alpha motor neuron

• B fibers: Slower myelinated (seldom used)B fibers: Slower myelinated (seldom used)

• C fibers: UnmyelinatedC fibers: Unmyelinated Slower conducting than As and smallest diameter (0.5 m/sec, 0.5 Slower conducting than As and smallest diameter (0.5 m/sec, 0.5 ))

Nerve Fiber Nerve Fiber ClassificationClassification

Sensory nerve classification (Lloyd-Hunt):Sensory nerve classification (Lloyd-Hunt):• I, II, III fibers: MyelinatedI, II, III fibers: Myelinated

Subtypes: Ia, IbSubtypes: Ia, Ib Fastest conducting and largest diameter – IaFastest conducting and largest diameter – Ia

• IV fibers: UnmyelinatedIV fibers: Unmyelinated Slower conducting than IIIs and smallest diameterSlower conducting than IIIs and smallest diameter

SYNAPSESYNAPSE Junction mediating information transfer from one Junction mediating information transfer from one

neuron to another neuron or an effector cellneuron to another neuron or an effector cell Axodendritic synapsesAxodendritic synapses

• Axonal endings Axonal endings dendrites of second neuron dendrites of second neuron Axosomatic synapsesAxosomatic synapses

• Axonal endings Axonal endings cell body of neuron cell body of neuron

Presynaptic neuronPresynaptic neuron• Conducts impulses toward the synapseConducts impulses toward the synapse

Postsynaptic neuronPostsynaptic neuron• Transmits impulse away from the synapseTransmits impulse away from the synapse

SYNAPSE TYPESSYNAPSE TYPESElectrical SynapsesElectrical Synapses Less common than chemical synapsesLess common than chemical synapses Correspond to gap junctions found elsewhereCorrespond to gap junctions found elsewhere

• Cytoplasm of adjacent neurons connected through Cytoplasm of adjacent neurons connected through protein channelsprotein channels

• Ions flow directly between neuronsIons flow directly between neurons• Neurons are Neurons are “electrically coupled”“electrically coupled”

Transmission across synapse is very rapidTransmission across synapse is very rapid

SYNAPSE TYPESSYNAPSE TYPESChemical SynapsesChemical Synapses Specialized for release & reception of Specialized for release & reception of

neurotransmittersneurotransmitters Two partsTwo parts

• Axonal terminal of presynaptic neuronAxonal terminal of presynaptic neuron Contains numerous synaptic vesicles filled with Contains numerous synaptic vesicles filled with

neurotransmitter moleculesneurotransmitter molecules

• Neurotransmitter receptor regionNeurotransmitter receptor region Present on dendrite or cell body of postsynaptic neuronPresent on dendrite or cell body of postsynaptic neuron

Separated by synaptic cleftSeparated by synaptic cleft• Remember this stuff in muscles?Remember this stuff in muscles?

SYNAPSESYNAPSE Nerve impulse reaches axonal terminalNerve impulse reaches axonal terminal Voltage-gated CaVoltage-gated Ca2+2+ channels open in axon channels open in axon

• CaCa2+2+ enters presynaptic neuron enters presynaptic neuron Neurotransmitter is released via exocytosisNeurotransmitter is released via exocytosis

• Vesicles fuse with axonal membraneVesicles fuse with axonal membrane Neurotransmitter binds to postsynaptic receptorsNeurotransmitter binds to postsynaptic receptors Ion channels open in Ion channels open in

postsynaptic membranepostsynaptic membrane• Result is excitation or Result is excitation or

inhibitioninhibition

SYNAPSESYNAPSE Binding of neurotransmitter to its receptor is Binding of neurotransmitter to its receptor is

reversiblereversible Permeability affected as long as neurotransmitter Permeability affected as long as neurotransmitter

is bound to its receptoris bound to its receptor Neurotransmitters do not persist in the synaptic Neurotransmitters do not persist in the synaptic

cleftcleft• Degraded by enzymes associated with postsynaptic Degraded by enzymes associated with postsynaptic

membranemembrane• Reuptake by astrocytes or presynaptic terminalReuptake by astrocytes or presynaptic terminal• Diffusion of neurotransmitters away from synapseDiffusion of neurotransmitters away from synapse

SYNAPSESYNAPSE Transmission of impulses along axon can be Transmission of impulses along axon can be

very fastvery fast• Up to 300 mph (150 m/s)Up to 300 mph (150 m/s)

Transmission of a signal across a synapse is Transmission of a signal across a synapse is slow in comparisonslow in comparison• Leads to Leads to “synaptic delay”“synaptic delay”• ~0.3 0 5.0 milliseconds~0.3 0 5.0 milliseconds• Rate-limiting step of neural transmissionRate-limiting step of neural transmission• Transmission along multisynaptic pathways is Transmission along multisynaptic pathways is

slower than along pathways with fewer synapsesslower than along pathways with fewer synapses

SYNAPSESYNAPSEPostsynaptic PotentialsPostsynaptic Potentials Many receptors present on postsynaptic Many receptors present on postsynaptic

membranes open ion channelsmembranes open ion channels• Ligand-gated channelsLigand-gated channels• Electrical signal converted to chemical signal Electrical signal converted to chemical signal

converted to electrical signalconverted to electrical signal• Graded potential is producedGraded potential is produced

Magnitude is dependent upon amount of neurotransmitter Magnitude is dependent upon amount of neurotransmitter releasedreleased

Action potential may be producedAction potential may be produced

• Either excitatory or inhibitoryEither excitatory or inhibitory

SYNAPSESYNAPSEExcitatory SynapsesExcitatory Synapses Neurotransmitter binding causes depolarizationNeurotransmitter binding causes depolarization

• Single type of channel opens in membraneSingle type of channel opens in membrane• NaNa++ and K and K++ simultaneously diffuse through the simultaneously diffuse through the

membrane in opposite directionsmembrane in opposite directions• NaNa++ influx exceeds K influx exceeds K++ efflux efflux• Net depolarization occursNet depolarization occurs• Local graded depolarization events formedLocal graded depolarization events formed

““Excitatory postsynaptic potential (EPSP)”Excitatory postsynaptic potential (EPSP)” May trigger an action potential at axon hillockMay trigger an action potential at axon hillock

• Voltage-gated channels at hillock open, etc.Voltage-gated channels at hillock open, etc.

SYNAPSESYNAPSEInhibitory SynapsesInhibitory Synapses Neurotransmitter binding reduces a postsynaptic Neurotransmitter binding reduces a postsynaptic

neuron’s ability to generate an action potentialneuron’s ability to generate an action potential• Increased permeability to KIncreased permeability to K++ and Cl and Cl--, not Na, not Na++

• Postsynaptic neuron becomes less likely to firePostsynaptic neuron becomes less likely to fire• ““Inhibitory postsynaptic potential (IPSP)”Inhibitory postsynaptic potential (IPSP)”

SYNAPSESYNAPSESummationSummation A single ESPS cannot induce an action potentialA single ESPS cannot induce an action potential

• Requires multiple axonal termini firing in concertRequires multiple axonal termini firing in concert Hundreds or thousands of EPSPs act togetherHundreds or thousands of EPSPs act together

• ““Summation”Summation”

Two types of summationTwo types of summation• Temporal summationTemporal summation

One or more neurons transmit in rapid successionOne or more neurons transmit in rapid succession

• Spatial summationSpatial summation Simultaneous stimulation by numerous termini from one Simultaneous stimulation by numerous termini from one

or more neuronsor more neurons

• (Both EPSPs and IPSPs summate)(Both EPSPs and IPSPs summate)

SYNAPSESYNAPSESynaptic PotentiationSynaptic Potentiation Repeated or continuous use of a synapse Repeated or continuous use of a synapse

enhances presynaptic neuron’s ability to exciteenhances presynaptic neuron’s ability to excite• Larger postsynaptic potentials producedLarger postsynaptic potentials produced• ““Synaptic potentiation”Synaptic potentiation”

Greater [Ca++] inside presynaptic terminalsGreater [Ca++] inside presynaptic terminals More neurotransmitter releasedMore neurotransmitter released Larger EPSPs producedLarger EPSPs produced

SYNAPSESYNAPSEPresynaptic InhibitionPresynaptic Inhibition Release of excitatory neurotransmitter can be Release of excitatory neurotransmitter can be

inhibited by activity of another neuroninhibited by activity of another neuron• Less neurotransmitter released and boundLess neurotransmitter released and bound

NEUROTRANSMITTERSNEUROTRANSMITTERS More than fifty neurotransmitters identifiedMore than fifty neurotransmitters identified Most neurons make two or moreMost neurons make two or more

• Can be released singly or togetherCan be released singly or together

Classification by StructureClassification by Structure Acetylcholine (ACh)Acetylcholine (ACh) Biogenic aminesBiogenic amines Amino acidsAmino acids PeptidesPeptides ATPATP Dissolved gasesDissolved gases

Classification by FunctionClassification by Function Excitatory/InhibitoryExcitatory/Inhibitory Direct/IndirectDirect/Indirect

NEURAL INTEGRATIONNEURAL INTEGRATION Neurons function in groups, not singlyNeurons function in groups, not singly These various components must interactThese various components must interact Multiple levels of neural integrationMultiple levels of neural integration

NEURONAL POOLSNEURONAL POOLS Neurons in CNS are organized into poolsNeurons in CNS are organized into pools

• Functional groupsFunctional groups• Integrate incoming informationIntegrate incoming information• Forward processed informationForward processed information

NEURONAL POOLSNEURONAL POOLSSimple Neuronal PoolSimple Neuronal Pool Incoming fiber branches profusely upon entering poolIncoming fiber branches profusely upon entering pool EPSPs induced in multiple postsynaptic neuronsEPSPs induced in multiple postsynaptic neurons EPSPs exceed threshold in some neuronsEPSPs exceed threshold in some neurons

• Mainly those with multiple synaptic contactsMainly those with multiple synaptic contacts EPSPs do not exceed EPSPs do not exceed

threshold in some threshold in some neuronsneurons• Mainly those with Mainly those with

fewer synaptic contactsfewer synaptic contacts

• Some close to thresholdSome close to threshold ““Facilitated zone”Facilitated zone”

TYPES OF CIRCUITSTYPES OF CIRCUITS Patterns of synaptic connections in neuronal Patterns of synaptic connections in neuronal

pools are called circuitspools are called circuits• Determine neuronal pool’s functional capabilitiesDetermine neuronal pool’s functional capabilities

Four basic circuit patternsFour basic circuit patterns• Diverging circuitsDiverging circuits• Converging circuitsConverging circuits• Reverberating (oscillating) circuitsReverberating (oscillating) circuits• Parallel after-discharge circuitsParallel after-discharge circuits

TYPES OF CIRCUITSTYPES OF CIRCUITSDiverging (Amplifying) CircuitDiverging (Amplifying) Circuit One incoming fiber triggers responses in ever-One incoming fiber triggers responses in ever-

increasing numbers of neuronsincreasing numbers of neurons Common in both sensory and motor systemsCommon in both sensory and motor systems

TYPES OF CIRCUITSTYPES OF CIRCUITSConverging CircuitsConverging Circuits Pool receives inputs from several neuronsPool receives inputs from several neurons Circuit has “funneling” effectCircuit has “funneling” effect Common in sensory Common in sensory

and motor systemsand motor systems

TYPES OF CIRCUITSTYPES OF CIRCUITSReverberating (Oscillating) CircuitsReverberating (Oscillating) Circuits Incoming signal travels through chain of Incoming signal travels through chain of

neuronsneurons Each neuron makes synapses with neurons Each neuron makes synapses with neurons

upstream in the pathwayupstream in the pathway Involved in rhythmic activities (e.g., breathing)Involved in rhythmic activities (e.g., breathing)

TYPES OF CIRCUITSTYPES OF CIRCUITSParallel After-Discharge CircuitsParallel After-Discharge Circuits Incoming fiber stimulated parallel neuron arraysIncoming fiber stimulated parallel neuron arrays Parallel arrays ultimately stimulate a common Parallel arrays ultimately stimulate a common

output celloutput cell• Create prolonged burst of impulsesCreate prolonged burst of impulses

Involved in complex Involved in complex mental processingmental processing

PROCESSING PATTERNSPROCESSING PATTERNS Serial input processingSerial input processing

• Input travels along one pathway to a specific Input travels along one pathway to a specific destinationdestination

• All-or-nothing function of systemAll-or-nothing function of system e.g., reflexese.g., reflexes

Parallel input processingParallel input processing• Inputs are segregated into multiple pathwaysInputs are segregated into multiple pathways

Integrated in different CNS regionsIntegrated in different CNS regions Different circuits do different things with inputDifferent circuits do different things with input

• Not repetitiousNot repetitious