11

Chapter 12Chapter 12

Lecture OutlineLecture Outline

See PowerPoint Image SlidesSee PowerPoint Image Slides

for all figures and tables pre-inserted intofor all figures and tables pre-inserted into

PowerPoint without notes.PowerPoint without notes.

Copyright (c) The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

22

Nervous TissueNervous Tissue

Overview of the nervous Overview of the nervous systemsystem

Nerve cells (neurons)Nerve cells (neurons) Supportive cells (neuroglia)Supportive cells (neuroglia) Electrophysiology of neuronsElectrophysiology of neurons SynapsesSynapses Neural integrationNeural integration

33

Overview of Nervous SystemOverview of Nervous System

Endocrine and nervous system maintain Endocrine and nervous system maintain internal coordinationinternal coordination endocrine = chemical messengers (hormones) endocrine = chemical messengers (hormones)

modifiers of the nervous systemmodifiers of the nervous system nervous response - three basic stepsnervous response - three basic steps

• sense organs receive informationsense organs receive information• brain and spinal cord determine responsesbrain and spinal cord determine responses• brain and spinal cord issue commands to glands brain and spinal cord issue commands to glands

and musclesand muscles

44

Subdivisions of Nervous SystemSubdivisions of Nervous System

Two major anatomical subdivisionsTwo major anatomical subdivisions Central nervous system (CNS)Central nervous system (CNS)

brain and spinal cord enclosed in bony brain and spinal cord enclosed in bony coveringscoverings

Peripheral nervous system (PNS)Peripheral nervous system (PNS) nerve = bundle of axons in connective tissuenerve = bundle of axons in connective tissue ganglion = swelling of cell bodies in a nerveganglion = swelling of cell bodies in a nerve

55

Subdivisions of Nervous SystemSubdivisions of Nervous System

66

Sensory (afferent) divisions Sensory (afferent) divisions visceral sensory and somatic sensory divisionvisceral sensory and somatic sensory division

Motor (efferent) division – 2 divisionsMotor (efferent) division – 2 divisions visceral motor division (ANS) visceral motor division (ANS)

effectors: cardiac, smooth muscle, glandseffectors: cardiac, smooth muscle, glands• sympathetic division (action)sympathetic division (action)• parasympathetic division (digestion)parasympathetic division (digestion)

somatic motor divisionsomatic motor division effectors: skeletal muscleeffectors: skeletal muscle

Functional Divisions of PNS

77

Subdivisions of Nervous System

88

Fundamental Types of NeuronsFundamental Types of Neurons

Sensory (afferent) neuronsSensory (afferent) neurons detect changes in body and external environmentdetect changes in body and external environment information transmitted into brain or spinal cordinformation transmitted into brain or spinal cord

Interneurons (association neurons)Interneurons (association neurons) lie between sensory and motor pathways in CNSlie between sensory and motor pathways in CNS 90% of our neurons are interneurons90% of our neurons are interneurons process, store and retrieve informationprocess, store and retrieve information

Motor (efferent) neuronMotor (efferent) neuron send signals out to muscles and gland cellssend signals out to muscles and gland cells organs that carry out responses called effectorsorgans that carry out responses called effectors

99

Fundamental Types of NeuronsFundamental Types of Neurons

1010

Properties of NeuronsProperties of Neurons

Excitability (irritability)Excitability (irritability) ability to respond to changes in the body and ability to respond to changes in the body and

external environment called stimuliexternal environment called stimuli ConductivityConductivity

produce traveling electrical signalsproduce traveling electrical signals SecretionSecretion

when electrical signal reaches end of nerve when electrical signal reaches end of nerve fiber, a chemical neurotransmitter is secretedfiber, a chemical neurotransmitter is secreted

1111

Structure of a NeuronStructure of a Neuron Cell body = perikaryon = Cell body = perikaryon =

somasoma single, central nucleus single, central nucleus cytoskeleton of cytoskeleton of

microtubules and microtubules and neurofibrils neurofibrils

• compartmentalizes compartmentalizes RER into Nissl bodiesRER into Nissl bodies

Vast number of short Vast number of short dendritesdendrites

for receiving signalsfor receiving signals

Singe axon (nerve fiber) Singe axon (nerve fiber) arising from axon hillock arising from axon hillock for rapid conductionfor rapid conduction

axoplasm and axolemma and axoplasm and axolemma and synaptic vesiclessynaptic vesicles

1212

A Representative NeuronA Representative Neuron

1313

Variation in Neural StructureVariation in Neural Structure Multipolar neuronMultipolar neuron

most commonmost common many dendrites/one many dendrites/one

axonaxon Bipolar neuronBipolar neuron

one dendrite/one axonone dendrite/one axon olfactory, retina, earolfactory, retina, ear

Unipolar neuronUnipolar neuron sensory from skin and sensory from skin and

organs to spinal cordorgans to spinal cord Anaxonic neuronAnaxonic neuron

many dendrites/no axonmany dendrites/no axon help in visual processeshelp in visual processes

1414

Types of Neuroglial Cells 1Types of Neuroglial Cells 1

Oligodendrocytes form myelin sheaths in Oligodendrocytes form myelin sheaths in CNSCNS each wraps around many nerve fiberseach wraps around many nerve fibers

Ependymal cells line cavities and produce Ependymal cells line cavities and produce CSFCSF

Microglia (macrophages) formed from Microglia (macrophages) formed from monocytesmonocytes in areas of infection, trauma or strokein areas of infection, trauma or stroke

1515

Types of Neuroglial Cells 2Types of Neuroglial Cells 2

AstrocytesAstrocytes most abundant glial cells - form framework of CNSmost abundant glial cells - form framework of CNS contribute to BBB and regulate composition of brain tissue fluidcontribute to BBB and regulate composition of brain tissue fluid convert glucose to lactate to feed neuronsconvert glucose to lactate to feed neurons secrete nerve growth factor promoting synapse formationsecrete nerve growth factor promoting synapse formation electrical influence on synaptic signalingelectrical influence on synaptic signaling sclerosis – damaged neurons replace by hardened mass of sclerosis – damaged neurons replace by hardened mass of

astrocytesastrocytes Schwann cells myelinate fibers of PNSSchwann cells myelinate fibers of PNS Satellite cells with uncertain functionSatellite cells with uncertain function

1616

Neuroglial Cells of CNSNeuroglial Cells of CNS

1717

Myelin 1Myelin 1

Insulating layer around a nerve fiberInsulating layer around a nerve fiber oligodendrocytes in CNS and schwann cells in oligodendrocytes in CNS and schwann cells in

PNSPNS formed from wrappings of plasma membraneformed from wrappings of plasma membrane

In PNS, hundreds of layers wrap axonIn PNS, hundreds of layers wrap axon the outermost coil is schwann cell (neurilemma)the outermost coil is schwann cell (neurilemma) covered by basal lamina and endoneuriumcovered by basal lamina and endoneurium

1818

Myelin 2Myelin 2

Oligodendrocytes myelinate several fibersOligodendrocytes myelinate several fibers Myelination spirals inward with new layers pushed Myelination spirals inward with new layers pushed

under the older onesunder the older ones

Gaps between myelin segments = nodes of Gaps between myelin segments = nodes of RanvierRanvier

Initial segment (area before 1st schwann cell) Initial segment (area before 1st schwann cell) and axon hillock form trigger zone where and axon hillock form trigger zone where signals beginsignals begin

1919

Myelin SheathMyelin Sheath

Note: Node of Ranvier between Schwann cellsNote: Node of Ranvier between Schwann cells

2020

Myelination in PNSMyelination in PNS

Myelination begins Myelination begins during fetal during fetal development, but development, but proceeds most rapidly proceeds most rapidly in infancy.in infancy.

2121

Unmyelinated Axons of PNSUnmyelinated Axons of PNS

Schwann cells hold small nerve fibers in grooves on their surface with Schwann cells hold small nerve fibers in grooves on their surface with only one membrane wrappingonly one membrane wrapping

2222

Myelination in CNSMyelination in CNS

2323

Speed of Nerve SignalSpeed of Nerve Signal

Diameter of fiber and presence of myelinDiameter of fiber and presence of myelin• large fibers have more surface area for signals large fibers have more surface area for signals

SpeedsSpeeds small, unmyelinated fibers = 0.5 - 2.0 m/secsmall, unmyelinated fibers = 0.5 - 2.0 m/sec small, myelinated fibers = 3 - 15.0 m/secsmall, myelinated fibers = 3 - 15.0 m/sec large, myelinated fibers = up to 120 m/seclarge, myelinated fibers = up to 120 m/sec

FunctionsFunctions slow signals supply the stomach and dilate pupilslow signals supply the stomach and dilate pupil fast signals supply skeletal muscles and transport sensory fast signals supply skeletal muscles and transport sensory

signals for vision and balancesignals for vision and balance

2424

Regeneration of Peripheral NervesRegeneration of Peripheral Nerves

Occurs if soma and neurilemmal tube is Occurs if soma and neurilemmal tube is intactintact

Stranded end of axon and myelin sheath Stranded end of axon and myelin sheath degeneratedegenerate

Axon stump puts out several sproutsAxon stump puts out several sprouts Regeneration tube guides lucky sprout Regeneration tube guides lucky sprout

back to its original destinationback to its original destination schwann cells produce nerve growth factorsschwann cells produce nerve growth factors

2525

Regeneration of Nerve FiberRegeneration of Nerve Fiber

2626

Electrical Potentials and CurrentsElectrical Potentials and Currents

Nerve pathway is a series of separate cellsNerve pathway is a series of separate cells Neural communication = mechanisms for Neural communication = mechanisms for

producing electrical potentials and currentsproducing electrical potentials and currents electrical potential - different concentrations of electrical potential - different concentrations of

charged particles in different parts of the cellcharged particles in different parts of the cell electrical current - flow of charged particles from electrical current - flow of charged particles from

one point to another within the cellone point to another within the cell Living cells are polarizedLiving cells are polarized

resting membrane potential is -70 mV with a resting membrane potential is -70 mV with a negative charge on the inside of membranenegative charge on the inside of membrane

2727

Resting Membrane PotentialResting Membrane Potential

Unequal electrolytes distribution between Unequal electrolytes distribution between ECF/ICFECF/ICF

Diffusion of ions down their concentration Diffusion of ions down their concentration gradientsgradients

Selective permeability of plasma membrane Selective permeability of plasma membrane Electrical attraction of cations and anionsElectrical attraction of cations and anions

2828

Resting Membrane Potential 2Resting Membrane Potential 2 Membrane very permeable to KMembrane very permeable to K++

leaks out until electrical gradient created attracts it leaks out until electrical gradient created attracts it back inback in

Membrane much less permeable to NaMembrane much less permeable to Na++

NaNa++/K/K++ pumps out 3 Na pumps out 3 Na++ for every 2 K for every 2 K++ it brings it brings inin works continuously and requires great deal of ATPworks continuously and requires great deal of ATP necessitates glucose and oxygen be supplied to necessitates glucose and oxygen be supplied to

nerve tissuenerve tissue

2929

Ionic Basis of Resting Membrane Ionic Basis of Resting Membrane PotentialPotential

NaNa++ concentrated outside of cell (ECF) concentrated outside of cell (ECF) KK++ concentrated inside cell (ICF) concentrated inside cell (ICF)

3030

Local Potentials 1Local Potentials 1

Local disturbances in membrane potential Local disturbances in membrane potential occur when neuron is stimulated by chemicals, occur when neuron is stimulated by chemicals,

light, heat or mechanical disturbancelight, heat or mechanical disturbance depolarization decreases potential across cell depolarization decreases potential across cell

membrane due to opening of gated Namembrane due to opening of gated Na++ channels channels • NaNa++ rushes in down concentration and electrical rushes in down concentration and electrical

gradientsgradients• NaNa++ diffuses for short distance inside membrane diffuses for short distance inside membrane

producing a change in voltage called a local potentialproducing a change in voltage called a local potential

3131

Local Potentials 2Local Potentials 2

Differences from action potentialDifferences from action potential are graded (vary in magnitude with stimulus are graded (vary in magnitude with stimulus

strength)strength) are decremental (get weaker the farther they are decremental (get weaker the farther they

spread)spread) are reversible as Kare reversible as K++ diffuses out of cell diffuses out of cell can be either excitatory or inhibitory can be either excitatory or inhibitory

(hyperpolarize)(hyperpolarize)

3232

Chemical ExcitationChemical Excitation

3333

Action PotentialsAction Potentials More dramatic change in membrane More dramatic change in membrane

produced where high density of voltage-gated produced where high density of voltage-gated channels occurchannels occur

trigger zone up to 500 channels/trigger zone up to 500 channels/mm2 2 (normal is 75)(normal is 75) If threshold potential (-55mV) is reached If threshold potential (-55mV) is reached

voltage-gated Navoltage-gated Na++ channels open (Na channels open (Na++ enters enters causing depolarization)causing depolarization)

Past 0 mV, NaPast 0 mV, Na+ + channels close = channels close = depolarizationdepolarization

Slow KSlow K++ gates fully open gates fully open KK++ exits repolarizing the cell exits repolarizing the cell Negative overshoot producesNegative overshoot produces

hyperpolarizationhyperpolarization excessive exiting of Kexcessive exiting of K++

3434

Action PotentialsAction Potentials

Called a spikeCalled a spike Characteristics of APCharacteristics of AP

follows an all-or-none law follows an all-or-none law • voltage gates either open or voltage gates either open or

don’tdon’t nondecremental (do not get nondecremental (do not get

weaker with distance)weaker with distance) irreversible (once started irreversible (once started

goes to completion and can goes to completion and can not be stopped)not be stopped)

3535

The Refractory PeriodThe Refractory Period Period of resistance to Period of resistance to

stimulationstimulation Absolute refractory periodAbsolute refractory period

as long as Naas long as Na++ gates are open gates are open no stimulus will trigger APno stimulus will trigger AP

Relative refractory periodRelative refractory period as long as Kas long as K++ gates are open gates are open only especially strong only especially strong

stimulus will trigger new APstimulus will trigger new AP Refractory period is occurring Refractory period is occurring

only to a small patch of only to a small patch of membrane at one time (quickly membrane at one time (quickly recovers)recovers)

3636

Impulse Conduction in Unmyelinated FibersImpulse Conduction in Unmyelinated Fibers

Threshold voltage in trigger zone begins Threshold voltage in trigger zone begins impulseimpulse

Nerve signal (impulse) - a chain reaction Nerve signal (impulse) - a chain reaction of sequential opening of voltage-gated Naof sequential opening of voltage-gated Na++ channels down entire length of axonchannels down entire length of axon

Nerve signal Nerve signal (nondecremental)(nondecremental) travels at travels at 2m/sec2m/sec

3737

Impulse Conduction - Unmyelinated FibersImpulse Conduction - Unmyelinated Fibers

3838

Saltatory Conduction - Myelinated FibersSaltatory Conduction - Myelinated Fibers

Voltage-gated channels needed for APsVoltage-gated channels needed for APs fewer than 25 per fewer than 25 per mm2 2 in myelin-covered regions in myelin-covered regions up to 12,000 per up to 12,000 per mm2 2 in nodes of Ranvierin nodes of Ranvier

Fast NaFast Na++ diffusion occurs between nodes diffusion occurs between nodes

3939

Saltatory ConductionSaltatory Conduction

Notice how the action potentials jump from Notice how the action potentials jump from node of Ranvier to node of Ranvier.node of Ranvier to node of Ranvier.

4040

Synapses between NeuronsSynapses between Neurons

First neuron releases neurotransmitter onto First neuron releases neurotransmitter onto second neuron that responds to itsecond neuron that responds to it 1st neuron is presynaptic neuron1st neuron is presynaptic neuron 2nd neuron is postsynaptic neuron2nd neuron is postsynaptic neuron

Synapse may be axodendritic, axosomatic or Synapse may be axodendritic, axosomatic or axoaxonicaxoaxonic

Number of synapses on postsynaptic cell Number of synapses on postsynaptic cell variablevariable 8000 on spinal motor neuron8000 on spinal motor neuron 100,000 on neuron in cerebellum100,000 on neuron in cerebellum

4141

Synaptic Relationships between Synaptic Relationships between NeuronsNeurons

4242

Chemical Synapse StructureChemical Synapse Structure

Presynaptic neurons have synaptic vesicles with Presynaptic neurons have synaptic vesicles with neurotransmitter and postsynaptic have receptorsneurotransmitter and postsynaptic have receptors

4343

Excitatory Cholinergic SynapseExcitatory Cholinergic Synapse Nerve signal opens voltage-Nerve signal opens voltage-

gated calcium channels gated calcium channels in synaptic knobin synaptic knob

Triggers release of ACh which Triggers release of ACh which crosses synapsecrosses synapse

ACh receptors trigger opening ACh receptors trigger opening of Naof Na++ channels producing channels producing local potential (postsynaptic local potential (postsynaptic potential)potential)

When reaches -55mV, triggers When reaches -55mV, triggers APAPin postsynaptic neuronin postsynaptic neuron

4444

Inhibitory GABA-ergic SynapseInhibitory GABA-ergic Synapse

Nerve signal triggers release of GABA Nerve signal triggers release of GABA

((-aminobutyric acid) which crosses -aminobutyric acid) which crosses synapsesynapse

GABA receptors trigger opening of ClGABA receptors trigger opening of Cl-- channels producing hyperpolarizationchannels producing hyperpolarization

Postsynaptic neuron now less likely to Postsynaptic neuron now less likely to reach thresholdreach threshold

4545

Excitatory Adrenergic SynapseExcitatory Adrenergic Synapse

Neurotransmitter is NE (norepinephrine)Neurotransmitter is NE (norepinephrine) Acts through 2Acts through 2ndnd messenger systems (cAMP) messenger systems (cAMP) cAMP has multiple effectscAMP has multiple effects

binds to ion gate inside of membrane binds to ion gate inside of membrane (depolarizing)(depolarizing)

activates cytoplasmic enzymesactivates cytoplasmic enzymes induces genetic transcription and production of induces genetic transcription and production of

new enzymesnew enzymes Its advantage is enzymatic amplificationIts advantage is enzymatic amplification

4646

Excitatory Adrenergic SynapseExcitatory Adrenergic Synapse

4747

Cessation and Modification of SignalCessation and Modification of Signal

Mechanisms to turn off stimulationMechanisms to turn off stimulation diffusion of neurotransmitter away into ECF diffusion of neurotransmitter away into ECF synaptic knob reabsorbs amino acids and synaptic knob reabsorbs amino acids and

monoamines by endocytosis monoamines by endocytosis acetylcholinesterase degrades ACh acetylcholinesterase degrades ACh

Neuromodulators modify transmissionNeuromodulators modify transmission raise or lower number of receptorsraise or lower number of receptors alter neurotransmitter release, synthesis or alter neurotransmitter release, synthesis or

breakdownbreakdown

4848

Neural IntegrationNeural Integration More synapses a neuron has the greater its More synapses a neuron has the greater its

information-processing capabilityinformation-processing capability cerebral cortex estimated to contain 100 trillion cerebral cortex estimated to contain 100 trillion

synapsessynapses Chemical synapses are decision-making Chemical synapses are decision-making

components of the nervous systemcomponents of the nervous system

Based on types of postsynaptic potentials Based on types of postsynaptic potentials produced by neurotransmittersproduced by neurotransmitters

4949

Postsynaptic Potentials- EPSPPostsynaptic Potentials- EPSP

Excitatory postsynaptic potentials (EPSP)Excitatory postsynaptic potentials (EPSP) a positive voltage change causing a positive voltage change causing

postsynaptic cell to be more likely to firepostsynaptic cell to be more likely to fire• result from Naresult from Na++ flowing into the cell flowing into the cell

glutamate and aspartate are excitatory glutamate and aspartate are excitatory neurotransmittersneurotransmitters

ACh and norepinephrine may excite or ACh and norepinephrine may excite or inhibit depending on cellinhibit depending on cell

5050

Postsynaptic Potentials- IPSPPostsynaptic Potentials- IPSP

Inhibitory postsynaptic potentials (IPSP)Inhibitory postsynaptic potentials (IPSP) a negative voltage change causing postsynaptic a negative voltage change causing postsynaptic

cell to be less likely to fire (hyperpolarize)cell to be less likely to fire (hyperpolarize)• result of Clresult of Cl-- flowing into the cell or K flowing into the cell or K++ leaving the cell leaving the cell

glycine and GABA are inhibitory glycine and GABA are inhibitory neurotransmittersneurotransmitters

ACh and norepinephrine may excite or inhibit ACh and norepinephrine may excite or inhibit depending upon celldepending upon cell

5151

Postsynaptic PotentialsPostsynaptic Potentials

5252

Summation - Postsynaptic PotentialsSummation - Postsynaptic Potentials Net postsynaptic potentials Net postsynaptic potentials

in trigger zonein trigger zone firing depends on net input of firing depends on net input of

other cellsother cells• typical EPSP voltage = 0.5 mV typical EPSP voltage = 0.5 mV

and lasts 20 msecand lasts 20 msec• 30 EPSPs needed to reach 30 EPSPs needed to reach

thresholdthreshold temporal summationtemporal summation

• single synapse receives single synapse receives many EPSPs in short timemany EPSPs in short time

spatial summationspatial summation• single synapse receives many single synapse receives many

EPSPs from many cellsEPSPs from many cells

5353

Summation of EPSP’sSummation of EPSP’s

Does this represent spatial or temporal summation?Does this represent spatial or temporal summation?

5454

Presynaptic InhibitionPresynaptic Inhibition

One presynaptic neuron suppresses anotherOne presynaptic neuron suppresses another neuron I releases inhibitory GABAneuron I releases inhibitory GABA

• prevents voltage-gated calcium channels from prevents voltage-gated calcium channels from opening -- it releases less or no neurotransmitter opening -- it releases less or no neurotransmitter

5555

Neural Circuits IllustratedNeural Circuits Illustrated

5656

Memory and Synaptic PlasticityMemory and Synaptic Plasticity

Physical basis of memory is a pathwayPhysical basis of memory is a pathway called a memory trace or engramcalled a memory trace or engram new synapses or existing synapses modified new synapses or existing synapses modified

to make transmission easier (synaptic to make transmission easier (synaptic plasticity)plasticity)

Synaptic potentiationSynaptic potentiation transmission mechanisms correlate with transmission mechanisms correlate with

different forms of memorydifferent forms of memory• Immediate, short and long-term memoryImmediate, short and long-term memory

5757

Immediate MemoryImmediate Memory

Ability to hold something in your thoughts Ability to hold something in your thoughts for just a few secondsfor just a few seconds Essential for reading abilityEssential for reading ability

Feel for the flow of events (sense of the Feel for the flow of events (sense of the present)present)

Our memory of what just happened Our memory of what just happened “echoes” in our minds for a few seconds“echoes” in our minds for a few seconds reverberating circuitsreverberating circuits

5858

Short-Term MemoryShort-Term Memory Lasts from a few seconds to several hoursLasts from a few seconds to several hours

quickly forgotten if distracted quickly forgotten if distracted Search for keys, dial the phoneSearch for keys, dial the phone

reverberating circuitsreverberating circuits Facilitation causes memory to last longerFacilitation causes memory to last longer

tetanic stimulation (rapid,repetitive signals) cause tetanic stimulation (rapid,repetitive signals) cause CaCa2+2+ accumulation and cells more likely to fire accumulation and cells more likely to fire

Posttetanic potentiation (to jog a memory)Posttetanic potentiation (to jog a memory) CaCa2+2+ level in synaptic knob stays elevated level in synaptic knob stays elevated little stimulation needed to recover memorylittle stimulation needed to recover memory

5959

Long-Term MemoryLong-Term Memory

Types of long-term memoryTypes of long-term memory declarative = retention of facts as textdeclarative = retention of facts as text procedural = retention of motor skills procedural = retention of motor skills

Physical remodeling of synapsesPhysical remodeling of synapses new branching of axons or dendrites new branching of axons or dendrites

Molecular changes = long-term Molecular changes = long-term tetanic stimulation causes ionic changestetanic stimulation causes ionic changes

• neuron produces more neurotransmitter receptorsneuron produces more neurotransmitter receptors

• more protein synthesizes for synapse remodelingmore protein synthesizes for synapse remodeling

• releases nitric oxide, then presynaptic neuron releases releases nitric oxide, then presynaptic neuron releases more neurotransmittermore neurotransmitter