The Nervous SystemThe Nervous System

Cell StructureCell Structure

Cells of the Central Nervous SystemCells of the Central Nervous System

Receiver (Receiver (AFFECTORAFFECTOR) cells from sense ) cells from sense organsorgans

Sender cells (Sender cells (EFFERENTEFFERENT) to motor ) to motor organs/musclesorgans/muscles

Also: Specialized “helper” cellsAlso: Specialized “helper” cells

Total Neurons: About 100 BillionTotal Neurons: About 100 Billion– Specialized nerve cells in CNS and PNSSpecialized nerve cells in CNS and PNS

NeuronsNeurons   Neurons: Specialized nerve cells in CNS and PNSNeurons: Specialized nerve cells in CNS and PNS

– Convey sensory information into the brainConvey sensory information into the brain– Carry out operations involved in thoughts, feeling, Carry out operations involved in thoughts, feeling,

behaviorbehavior– Transmit commands to body to control muscles and Transmit commands to body to control muscles and

organsorgans– Many different specializationsMany different specializations

Many neurons:Many neurons:– 26-29 billion in higher brain areas26-29 billion in higher brain areas– 70 billion in cerebellum70 billion in cerebellum– 1 billion in spinal cord1 billion in spinal cord

Parts of a NeuronParts of a Neuron SomaSoma: :

– regulates life functions (metabolism)regulates life functions (metabolism)

– Contains nucleus (and chromosomes), organelles, etc.Contains nucleus (and chromosomes), organelles, etc.

DendritesDendrites: : – branched projections from soma branched projections from soma

– receive transmissions from   other neuronsreceive transmissions from   other neurons

AxonAxon: : –     long projection extending from somalong projection extending from soma

–     transmits information to next neurontransmits information to next neuron

–     axon hillock: beginning of axon, important in transmissionaxon hillock: beginning of axon, important in transmission

Parts of a NeuronParts of a Neuron TerminalsTerminals or Terminal Buttonsor Terminal Buttons

– bulbs on end of branched portion of axonbulbs on end of branched portion of axon

– synaptic bulbs or terminalssynaptic bulbs or terminals

– contain neurotransmitterscontain neurotransmitters

Synapse or synaptic cleftSynapse or synaptic cleft–     space between neuronsspace between neurons

–     space between one neuron's synaptic bulb/other's dendritesspace between one neuron's synaptic bulb/other's dendrites

Myelin sheath: Myelin sheath: – glue like structures that hold neurons in placeglue like structures that hold neurons in place

Myelin SheathMyelin Sheath     insulates neuronsinsulates neurons

    made of glial cells or “glue cells”made of glial cells or “glue cells”

– In CNS: In CNS: oligodendroglial cellsoligodendroglial cells

– In PNS: In PNS: Schwann cellsSchwann cells

    allows synaptic transmission to occur by jumping down axonallows synaptic transmission to occur by jumping down axon

    exposed area between sheath = exposed area between sheath = Nodes of RanvierNodes of Ranvier

Several kinds of neurons Several kinds of neurons and helper cellsand helper cells

Affector or Receptor neuronsAffector or Receptor neurons::– SENSORY neurons: embedded in sense organsSENSORY neurons: embedded in sense organs– specialized to receive stimulation from environment and specialized to receive stimulation from environment and

send to the brainsend to the brain

May be May be UNIPOLAR or BIPOLARUNIPOLAR or BIPOLAR– Single axonSingle axon– Two axons: end of axon branches into twoTwo axons: end of axon branches into two

Axon and dendrites extend in several directions from Axon and dendrites extend in several directions from bodybody

Several kinds of neurons Several kinds of neurons and helper cellsand helper cells

Effector or Motor neuronsEffector or Motor neurons– specialized to contract muscles and stimulate specialized to contract muscles and stimulate

 glandular secretions glandular secretions– acted upon by nerves and neuronsacted upon by nerves and neurons

MULTIPOLARMULTIPOLAR: have multiple axons which : have multiple axons which extend from soma in several directionsextend from soma in several directions– Dendrites on one end; axon on otherDendrites on one end; axon on other

Several kinds of neuronsSeveral kinds of neuronsand helper cellsand helper cells

InterneuronsInterneurons– Connect one neuron to another in same part or Connect one neuron to another in same part or

region of brain/spinal cordregion of brain/spinal cord

– MultipolarMultipolar

– Seem to be missing the axon (it is very short or Seem to be missing the axon (it is very short or nonexistent)nonexistent)

Several kinds of neuronsSeveral kinds of neuronsand helper cellsand helper cells

Glial cells: form the myelin sheathGlial cells: form the myelin sheath– Wrap around on outside of most human neurons:Wrap around on outside of most human neurons:

Insulate and wrap around neurons:Insulate and wrap around neurons:– Speeds up neural transmissionSpeeds up neural transmission– Also help with storing of neurotransmitterAlso help with storing of neurotransmitter– Important part of waste system for neuron as wellImportant part of waste system for neuron as well

Multiple Sclerosis = allergy to own myelinMultiple Sclerosis = allergy to own myelin

Neural Membrane Neural Membrane and Its potential:and Its potential:

HOW THE NEURON WORKSHOW THE NEURON WORKS

The Cell MembraneThe Cell Membrane Cell membrane = Cell membrane =

– The cell wall or “skin” of the cellThe cell wall or “skin” of the cell– most critical factor in neural communicationmost critical factor in neural communication– Only about 8 micrometers ( 8 millionths of a meter) thickOnly about 8 micrometers ( 8 millionths of a meter) thick

Composed of lipid (fat) and proteinComposed of lipid (fat) and protein– Lipid molecules arranged Lipid molecules arranged head to tailhead to tail– Heads are water soluable (attract water)Heads are water soluable (attract water)– Tails are water insoluable (repel water)Tails are water insoluable (repel water)

Heads point towards surrounding fluid, tails turn awayHeads point towards surrounding fluid, tails turn away– This creates double layer membraneThis creates double layer membrane

Neuron lipid layerNeuron lipid layer

Neuron PotentialsNeuron Potentials Membrane holds cell togetherMembrane holds cell together

– More importantly: CONTROLS environment within and outside More importantly: CONTROLS environment within and outside cellcell

SemipermeableSemipermeable: : – allows some molecules in/outallows some molecules in/out– HH220; O0; O22, CO, CO22 pass freely pass freely

Selective permeabilitySelective permeability::– Keeps out some substancesKeeps out some substances– Allows others in only under certain circumstancesAllows others in only under certain circumstances– Protein channels: open and close to let molecules in when Protein channels: open and close to let molecules in when

neuron is activeneuron is active

Neuron PotentialNeuron Potential Polarization is result of this selective membrane Polarization is result of this selective membrane

permeability: permeability: – means that the cell has an electrical chargemeans that the cell has an electrical charge

PotentialPotential: difference in electrical charge between the : difference in electrical charge between the inside and outside of a cell (or any two points)inside and outside of a cell (or any two points)

Neuron has Neuron has three critical potentialsthree critical potentials::– Resting Resting potential: cell is at restpotential: cell is at rest– ActionAction potential: cell is active and sending a signal potential: cell is active and sending a signal– RefractoryRefractory potential: cell is recovering potential: cell is recovering

  Resting potentialResting potential Neurons sit at base level: Neurons sit at base level: RESTING POTENTIALRESTING POTENTIAL

– Resting potential = approximately Resting potential = approximately -70 -70 mVmV

Why -70 mV?Why -70 mV?– 70 mV charge due to unequal distribution of electrical charges on 70 mV charge due to unequal distribution of electrical charges on

two sides of cell membrane:two sides of cell membrane:

– inside of axon is negatively chargedinside of axon is negatively charged: : more K+ ; more A-more K+ ; more A-

– outside of axon is positively chargedoutside of axon is positively charged: : More Na+; some Cl-More Na+; some Cl-

Remember: Remember: axon has voltage of -70mV at resting axon has voltage of -70mV at resting potentialpotential

How can neuron stabilize at resting potential?How can neuron stabilize at resting potential?

DiffusionDiffusion: Molecules diffuse from area of high concentration to low : Molecules diffuse from area of high concentration to low concentration until “evened out”:concentration until “evened out”:

Concentration gradientConcentration gradient: ions move to side of membrane where less : ions move to side of membrane where less concentratedconcentrated

Electrical gradientElectrical gradient: ions attracted to side that is of opposite charge: ions attracted to side that is of opposite charge

Other factors upset this diffusion:Other factors upset this diffusion:– Neuron wall Neuron wall semi permeablesemi permeable: anions too large to pass through membrane: anions too large to pass through membrane– Negative charge of anions repels Cl- ions so they don’t move insideNegative charge of anions repels Cl- ions so they don’t move inside

During an ACTION POTENTIALDuring an ACTION POTENTIAL, membrane undergoes changes:, membrane undergoes changes:– opens gates into/out of cellopens gates into/out of cell– Results in changes to the t charge of the concentration Results in changes to the t charge of the concentration

Na+K+ Pump or Ion PumpNa+K+ Pump or Ion Pump K+ and Na+ are specialK+ and Na+ are special::

– K+ tends to move out of cellK+ tends to move out of cell concentration gradient is stronger than electrical gradientconcentration gradient is stronger than electrical gradient

– Na+ tends to move into cell: Na+ tends to move into cell: both gradients pull Na+ insideboth gradients pull Na+ inside

K+ and Na+ pass through membrane via K+ and Na+ pass through membrane via special protein channelsspecial protein channels– Most Na+ and K+ remain in place during resting Most Na+ and K+ remain in place during resting

potentialpotential– Those that do get through are returned via NA+K+ Those that do get through are returned via NA+K+

pumppump

• Na+ K ion pump = large protein molecules that move Na+ ions to outside/K+ to inside

• Rate of exchange: 3 Na+/2 K+

• Maintains membrane as more negative inside than out

• Metabolic process: uses energy (about 40% of energy expenditure of the cell!)

Na+K+ Pump or Ion Pump

Neuron PotentialNeuron Potential Polarization is result of this selective membrane Polarization is result of this selective membrane

permeability: permeability: – means that the cell has an electrical chargemeans that the cell has an electrical charge

PotentialPotential: difference in electrical charge between the : difference in electrical charge between the inside and outside of a cell (or any two points)inside and outside of a cell (or any two points)

Neuron has Neuron has three critical potentialsthree critical potentials::– Resting Resting potential: cell is at restpotential: cell is at rest– ActionAction potential: cell is active and sending a signal potential: cell is active and sending a signal– RefractoryRefractory potential: cell is recovering potential: cell is recovering

Action PotentialAction Potential Action potential Action potential = = abrupt depolarization abrupt depolarization

of membrane that allows neuron to of membrane that allows neuron to communicate over long distancescommunicate over long distances

Neuron becomes excited and sends a signal Neuron becomes excited and sends a signal via neurotransmitter releasevia neurotransmitter release

    if incoming message is sufficient in if incoming message is sufficient in strength: Causes an ACTION POTENTIALstrength: Causes an ACTION POTENTIAL

Action PotentialAction Potential

DendritesDendrites (usually) (usually) receivereceive incoming neurotransmitter incoming neurotransmitter– Chemical fits in “lock” on dendriteChemical fits in “lock” on dendrite– Alters the shape of the cell wallAlters the shape of the cell wall

PARTIAL DEPOLARIZATION at dendritesPARTIAL DEPOLARIZATION at dendrites: : – Allows changes in cell wall that will change voltage inside the Allows changes in cell wall that will change voltage inside the

neuronneuron

– THIS depolarization Is THIS depolarization Is decrementeddecremented: decreases with : decreases with time/distancetime/distance

– Also called Also called local potential local potential because has only a local effectbecause has only a local effect

  

Action PotentialAction Potential All or None LawAll or None Law: Voltage change is either sufficient to : Voltage change is either sufficient to

stimulate action potential, or stimulate action potential, or not (no wimpy action potentials!)not (no wimpy action potentials!)

Voltage changes from Voltage changes from -70 to +40 mV -70 to +40 mV and back againand back again

This This “depolarization” begins “depolarization” begins at the at the axon hillockaxon hillock–       inside of axon becomes negative due to movement of ionsinside of axon becomes negative due to movement of ions

     NaCl goes out of axonNaCl goes out of axon       outside of axon becomes positive: K+ goes inoutside of axon becomes positive: K+ goes in

–       result is voltage change as switching of ions occursresult is voltage change as switching of ions occurs

    depolarization moves down axon in wavelike form in depolarization moves down axon in wavelike form in myelinated neuronsmyelinated neurons

The Neuron FiresThe Neuron Fires Voltage across cell membrane is stored energy; if this Voltage across cell membrane is stored energy; if this

stored energy is released, get tremendous changes within stored energy is released, get tremendous changes within cellcell

During action potential: Na+ channels openDuring action potential: Na+ channels open– Remember: thousands of Na+ ions held on outside- now they Remember: thousands of Na+ ions held on outside- now they

rush in through these channelsrush in through these channels

– Approximately Approximately 500x greater 500x greater than normal number of Na+ ionsthan normal number of Na+ ions

– Small area inside Small area inside membrane is depolarizedmembrane is depolarized, first to 0 and then , first to 0 and then to +30 to +40mVto +30 to +40mV

– This small area will then spread down axon: cell wall opens and This small area will then spread down axon: cell wall opens and ion exchange occurs at Nodes of Ranvierion exchange occurs at Nodes of Ranvier

As reach peak of Action PotentialAs reach peak of Action Potential K+ ions move out due to diffusion.K+ ions move out due to diffusion.

K+ also moves out due to electrostatic pressure because K+ also moves out due to electrostatic pressure because the inside of the cell is temporarily positive.the inside of the cell is temporarily positive.

Membrane returns to near resting potential or Membrane returns to near resting potential or BELOWBELOW

This entire event takes approximately This entire event takes approximately 1 millisecond1 millisecond..

Because nearby sodium channels open, a new action Because nearby sodium channels open, a new action potential is triggered at the adjacent patch of membrane. potential is triggered at the adjacent patch of membrane.

Refractory PeriodRefractory Period Absolute refractory period: Neuron repolarizes Absolute refractory period: Neuron repolarizes

– cell environment moves back toward resting potential during cell environment moves back toward resting potential during refractory periodrefractory period

– Resetting neuron back to resting potentialResetting neuron back to resting potential

– Cell absolutely cannot fire during this periodCell absolutely cannot fire during this period

Then Then Relative Refractory periodRelative Refractory period: : – Neuron can fire, Neuron can fire,

– but only with extra stimulationbut only with extra stimulation

Absolute Refractory PeriodAbsolute Refractory Period Neuron Neuron cannot fire cannot fire during this periodduring this period

Due to action of Ion pump:Due to action of Ion pump:– Ion pump kicks into action at end of action potentialIon pump kicks into action at end of action potential

– Pumps ions Pumps ions K+ in and Na+ outK+ in and Na+ out

– Over does it a bit: cell ends up just below resting potentialOver does it a bit: cell ends up just below resting potential

– Until returns to resting potential, very difficult, if not impossible, for Until returns to resting potential, very difficult, if not impossible, for cell to firecell to fire

Important functions of Important functions of Absolute Refractory PeriodAbsolute Refractory Period

When the Na+ channels close during the When the Na+ channels close during the action potential, that part of the axon action potential, that part of the axon cannot fire again.cannot fire again.

This limits how frequently the neuron can This limits how frequently the neuron can fire.fire.

This also prevents backward spread of This also prevents backward spread of depolarization, so action potentials move depolarization, so action potentials move only toward the terminals.only toward the terminals.

Important functions of Important functions of Relative Refractory PeriodRelative Refractory Period

Plays role in Plays role in intensity coding intensity coding in axonin axon

K+ channels open for just milliseconds longer K+ channels open for just milliseconds longer following absolute refractory periodfollowing absolute refractory period

Makes inside of cell slightly more negative; harder to Makes inside of cell slightly more negative; harder to firefire

Rate law: Rate law: Stronger stimuli trigger new action Stronger stimuli trigger new action potentials earlier in recovery, so the axon encodes potentials earlier in recovery, so the axon encodes intensity as rate of firing.intensity as rate of firing.

Thus: Thus: only stronger stimulation can set off neurononly stronger stimulation can set off neuron

Remember:Remember: Movement of action potentials down the axon Movement of action potentials down the axon

is not a flow of ions but a chain of events.is not a flow of ions but a chain of events.

Because the action potential “jumps” from node Because the action potential “jumps” from node to node this is called to node this is called saltatory conduction.saltatory conduction.

When the action potential reaches the When the action potential reaches the terminals it passes the message on to the next terminals it passes the message on to the next cell “in line”…..and it begins againcell “in line”…..and it begins again

Nondecremental conductionNondecremental conduction Action potential different from Action potential different from local potential local potential in in

several important ways:several important ways:

– Local potential = graded potentialLocal potential = graded potential- it varies in magnitude - it varies in magnitude depending on strength of stimulus that produced it; depending on strength of stimulus that produced it; action potential is ungradedaction potential is ungraded

– Action potential obeys all or none lawAction potential obeys all or none law: occurs at full : occurs at full strength or not at allstrength or not at all

Action potential is Action potential is nondecrementalnondecremental: does NOT lose : does NOT lose strength at each successive point (local potentials strength at each successive point (local potentials do degrade)do degrade)

Neurotoxins and Ion channelsNeurotoxins and Ion channels Neurotoxins affect ion channels involved in the action potential.Neurotoxins affect ion channels involved in the action potential.

The puffer fish produces The puffer fish produces tetrodotoxintetrodotoxin: blocks sodium channels.: blocks sodium channels.

Scorpion venom Scorpion venom keeps sodium channels open, prolonging the keeps sodium channels open, prolonging the action potential.action potential.

Beneficial drugs Beneficial drugs affect these ion channels as well.affect these ion channels as well.– Local anesthetics block sodium channels.Local anesthetics block sodium channels.– Some general anesthetics work by opening potassium channels.Some general anesthetics work by opening potassium channels.

Ion channels can be modified to control neurons by light.Ion channels can be modified to control neurons by light.– This allows greater precision in stimulating neurons and identifying This allows greater precision in stimulating neurons and identifying

pathways in the brain.pathways in the brain.

Again: Three Steps for firingAgain: Three Steps for firing Resting potentialResting potential: voltage is about -70mV: voltage is about -70mV

– Dendrites receive incoming signalsDendrites receive incoming signals– If sufficient, cell goes into firing modeIf sufficient, cell goes into firing mode

Action potentialAction potential– Voltage changes from -70mV to +40mVVoltage changes from -70mV to +40mV– Ions exchange placesIons exchange places– Repeats itself rapidly down axonRepeats itself rapidly down axon– Only in places where myelin sheath doesn’t cover: Nodes of RanvierOnly in places where myelin sheath doesn’t cover: Nodes of Ranvier

Refractory PeriodRefractory Period: : – below resting or lower than -70mVbelow resting or lower than -70mV– Cell recovers from firingCell recovers from firing– Absolute refractor period: Brief time period when cannot fire againAbsolute refractor period: Brief time period when cannot fire again– Relative refractory period: Brief time period when difficult for it to fire again.Relative refractory period: Brief time period when difficult for it to fire again.

Take home lesson:Take home lesson:– Axon encodes stimulus intensity by controlling FIRING RATE not size Axon encodes stimulus intensity by controlling FIRING RATE not size

of action potentialof action potential

Why so fast?Why so fast?Thank your Glial cellsThank your Glial cells

• Remember: Glial cells: Remember: Glial cells: – Non neural cellsNon neural cells– Provide a supporting function to neuronsProvide a supporting function to neurons– Account for 90% of cells in adult human brainAccount for 90% of cells in adult human brain

• Function: Help hold neurons together, assist in Function: Help hold neurons together, assist in neurotransmissionneurotransmission– Provide supports for the nervous systemProvide supports for the nervous system

– In periphery are rather rigid: In periphery are rather rigid: • E.g., Schwann cellsE.g., Schwann cells

– In CNS: are soft and squishy:In CNS: are soft and squishy:• E.g., Oligodenroglia cellsE.g., Oligodenroglia cells

Glial Cells speed conductionGlial Cells speed conduction• Neurons conduct impulses from 1 to 120 meters/sec or 270 mphNeurons conduct impulses from 1 to 120 meters/sec or 270 mph

– Still fairly slowStill fairly slow

Since reaction time critical for survival, body found ways to Since reaction time critical for survival, body found ways to increase conduction speedincrease conduction speed

• Vary thickness of axons to provide less resistanceVary thickness of axons to provide less resistance• Motor neurons: diameter of 0.5 mm can attain conduction speed of Motor neurons: diameter of 0.5 mm can attain conduction speed of

30m/sec30m/sec

• But: conduction speed not increase in direct proportion to size: is But: conduction speed not increase in direct proportion to size: is power function, thus must find alternative waypower function, thus must find alternative way

Alternative way: use graded local potentialsAlternative way: use graded local potentials

Myelination = solution to increasing Myelination = solution to increasing speed of neural transmissionspeed of neural transmission

• Vertebrates are myelinated: allows Vertebrates are myelinated: allows SALTATORY conductionSALTATORY conduction

– Action potential jumps from node to nodeAction potential jumps from node to node

– Myelin also helps increase speed via Myelin also helps increase speed via capacitance: resists movement of ions during capacitance: resists movement of ions during graded potentialgraded potential

Overall effect: 100x greater conduction Overall effect: 100x greater conduction speed; reduced work for Ion pumpspeed; reduced work for Ion pump

Other functions of Glial CellsOther functions of Glial Cells Important in fetal development: scaffold that guides new Important in fetal development: scaffold that guides new

neurons to destinationneurons to destination

Provide energy to cellProvide energy to cell

Serve as waste system for neuronsServe as waste system for neurons

Aid in development and maintenance of neural Aid in development and maintenance of neural connectionsconnections– Get 7x more connections when glial cells availableGet 7x more connections when glial cells available

Help in conducting action potentialHelp in conducting action potential

Now: Why an action potential?Now: Why an action potential? Allows release of neurotransmitterAllows release of neurotransmitter

Neurotransmitter is a chemical substanceNeurotransmitter is a chemical substance– Remember: even chemical substances contain a Remember: even chemical substances contain a

chargecharge

Several specific kinds- each act on certain Several specific kinds- each act on certain neuronsneurons

Most neurons respond to and release one kind Most neurons respond to and release one kind of neurotransmitterof neurotransmitter

Now: Why an action potential?Now: Why an action potential? Neurotransmitter stored in synaptic vesiclesNeurotransmitter stored in synaptic vesicles

• Remember, these are at the END of the axonRemember, these are at the END of the axon• Next to the synapseNext to the synapse

Action potential opens channels that allow Ca+ ions to enter Action potential opens channels that allow Ca+ ions to enter terminals from extracellular fluidterminals from extracellular fluid

– Ca+ ions cause vesicles nearest the membrane to fuse Ca+ ions cause vesicles nearest the membrane to fuse with membranewith membrane

– Membrane then opens and transmitter is dumped into Membrane then opens and transmitter is dumped into synapsesynapse

Neurotransmitter then diffuses across synapse to Neurotransmitter then diffuses across synapse to postsynaptic neuron and attaches to chemical receptorpostsynaptic neuron and attaches to chemical receptor– And if enough NT moves across, it all starts again! And if enough NT moves across, it all starts again!