1.2. neurophysiology-conduction, transmission, and the integration of neural signals (slide...

7/31/2019 1.2. Neurophysiology-Conduction, Transmission, And the Integration of Neural Signals (Slide Presentation)

1/70

Chapter 3: Neurophysiology: Conduction, Transmission,and the Integration of Neural Signals

> Communication Within a Neuron

> Communication Between Neurons

copyright D.P. Devine


2/70

> Electricity:

negative pole = greater number of electrons, greater negative charge

positive pole = fewer electrons, less negative charge

current = flow of electrons from negative to positive pole (measured in amperes)

electrical potential = difference in electrical charge (measured in volts)

between negative and positive poles

Communication Within a Neuron

> Recording the Membrane

Potential of a Neuron:

Resting Potential = -70mV

(varies from one neuron to another)


3/70

> Stimulating the Neuronal Membrane

with a Microelectrode:

Communication Within

a Neuron


4/70

> Stimulate with

microelectrode> Record with secondmicroelectrode

> HyperpolarizationApply small negativecurrent to increasenegative membranepotential

0

-20

-40-60

-80

-100


time (ms)


5/70

> Depolarization

Apply depolarizingcurrent to decreasemembrane potentialtoward neutrality

0

-20

-40-60

-80

-100

> Stimulate with

microelectrode> Record with secondmicroelectrode


time (ms)


6/70

> Depolarization:

Apply a slightly largerdepolarizing current to reach-55mV threshold

> Action Potential:

A disproportionately

large response,constant regardless ofmagnitude of stimulation

above -55mV

20

0

-20-40

-80

-120

All - or - none


time (ms)


7/70

> Concentration Gradient:- Molecules are in constant motion.- In the absence of external forces or

barriers, molecules diffuse accordingto their concentration gradient.



8/70

> Voltage Gradient / Electrostatic Potential:- Electrolytes dissociate into ions in solution.- For example, NaCl dissociates into Na+

(a cation) and Cl-

(an anion)..- Like ions (i.e. those with the same charge)

will repel each other in solution.Na+

Na+

Na+

Na+

Cl-

Cl-

Cl-

Cl-



9/70

> Dispersion of charged particles with an impermeable and asemipermeable membrane:



10/70

> Positive ions (cations):

sodium (Na+), potassium (K+)

> Negative ions

(anions):

chloride (Cl-),

proteins

-

--

-+

+

+

++ +

+


Ion Exchange


11/70

+

+

> Channel proteins: Cylindrical proteins that permitcontrolled exchange of ions across the membrane.

++

+

+

+

+

+

-

-

-

-

-

-

-

+

+

+

+

+

+

++


Ion Exchange


12/70

> Resting potential: In the absence of disturbance themembrane maintains a slightly negative electrical

potential (i.e.balanceof ionic charges) insidethe neuron, with

respect to the outside. +

+

++

+

+

+

+

+

-

--

-

-

-

-


Ion Exchange


13/70

> Sodium (Na+): More than ten times more concentrated outsidethe cell (extracellular) than inside the cell (intracellular)

Na+

Na+Na+ Na+

Na+

Na+

Na+Na

+

Na+

Na+

Na+ Na+Na+ Na+ Na+

Na+Na+

Na+

Na+

Na+Na+ Na

+

Na+

Na+

Na+Na+

Na+Na+

Na+

Na+

Na+Na+

Na+

Na+

Na+

Na+


Ion Exchange


14/70

> Potassium (K+): More than twenty times more concentratedinside the cell (intracellular) than outside the cell (extracellular)

K+

K+

K+K+

K+K+

K+K+

K+

K+K+

K+

K+

K+

K+

K+

K+ K+K+

K+

K+

K+


Ion Exchange


15/70

Na+

> [Na+] > [K+]: There are many more sodium ions thanpotassium ions, providing a net positive extracellular potential.

K+

K+

K+K+

K+K+

K+K+

K+

K+K+

K+

K+

K+

K+

K+

K+ K+K+

K+

K+

Na+

Na+

Na+ Na+Na+ Na+

Na+

Na+

Na+Na+ Na

+

Na+

Na+

Na+Na+Na+

Na+

Na+

Na+Na+

Na+Na+

Na+

Na+

Na+Na+ Na+

Na+

Na+Na+

Na+Na

+Na+

Na+

K+


Ion Exchange


16/70

Cl-

Cl-

Cl-

Cl-Cl-

Cl-

> Chloride (Cl-): More concentrated in the extracellular spacethan the intracellular space

Cl-

Cl-Cl-

Cl-Cl-

Cl-


Ion Exchange


17/70


18/70

> Resting Potential: Difference between the net charge(considering all the positive and negative charges) inside

the cell, relative tothe net charge outsidethe cell (approx.

-70mV in the giantsquid axon).

Na+

Na+Na+

Na+Na+

Na+

Na+

Na+

Na+Na+ Na

+

Na+

Cl-

Cl-

Cl-

Cl-Cl-

Cl-

K+

K+

K+

K+

AAA

AAA

AA

AAA

AA

AAAAAAAA

AAAAA

AAAAAA

AA A

AAAA


Ion Exchange


19/70

> Selective Permeability: Some molecules can freely cross thecell membrane (e.g. O2, CO2, urea, water).

Most larger molecules (e.g. negatively charged proteins) andions (e.g. Na+) are prevented from freely crossing the

membrane.

CO2

CO2CO2

CO2

urea

ureaurea

urea

H2O H2O

H2O

H2O

O2

O2

O2

O2

O2

O2

H2O

H2OH2O

H2O

Na+ Na+

Na+

Na+

AAAAAA

AA A

AAAAAAAAAA

AA AAAAA


Ion Exchange

intracellular extracellular


20/70

Sodium-Potassium Pump:Na+ and K+ are actively transportedacross the membrane by specific Na+/K+ transport proteins

> Na+

:Na+

/K+

pump actively transports 3 Na+

out of the cell.Na+ concentration gradient would push Na+back in.Electrical gradient would push Na+back in.BUT the membrane is almost impermeable to Na+.

> K+:Na+/K+pump actively transports2 K+ into the cell.

K+ concentration gradient would push

K+back out.The membrane is semipermeable toK+, so K+ could leak back out.

BUT the electrical gradient keeps

K+ inside the cell.

Communication Within a NeuronIon Exchange

membrane

Na+-K+

transporter

extracellular

intracellular

3 Na+ out

2 K+ in

Na+ Na+

Na+

K+ K+


21/70

+

-

At Resting Potential

Summary of Forces on Charged Particles


membrane

extracellular

intracellular

+

-

+

-

+

-

+

-

+

--

+

-

+

proteins-

cannotleave cell

K+

force ofdiffusion

electrostaticpressure

K+low

conc Cl-

force ofdiffusion


Cl-

Na+

force ofdiffusion


Na+

highconc

highconc

lowconc


22/70

Hyperpolarization and Depolarization



23/70

> Extremely high energy expenditure: Very energyexpensive, approximately 40% of neurons energy

resources

20

0

-20

-40

-80-120

> Extremely rapid, strong response: By maintaining a highconcentration gradient and electrostatic potential, the neuron

is prepared to exert a very rapid and powerful response whencalled upon - THE ACTION POTENTIAL!!


Why a Resting Potential?

time (ms)


24/70

> Axon Hillock:

Electrochemical input from

soma arrives at axon hillock.If above threshold, actionpotential is initiated.

20

0

-20

-40

-80-120

All - or - none

Axon hillock

Axon

Soma

Dendrites

The Action Potential and the Axon Hillock


time (ms)


25/70

The All-Or-None-Law


For all stimuli that exceed threshold

The size and shape of the action potential are independent of theintensity of the stimulus that initiated it.


26/70

> Voltage-Gated Ion Channels:

Respond by opening or closing

according to the value of themembrane potential

> At -70 to -55mV

Some Na+ channels openSmall Na+ influxSome K+ channels openSmall K+ effluxDriven by conc. gradient

& electrostatic pressure.


The Action Potential


27/70




> At -55mV

Na+ channels openNa+ rushes inK+ channels openK+ exitsDriven by conc. gradient

& electrostatic pressure.




28/70




> Depolarization &

Reverse Polarization

Rapid change inmembranepotential from-70mV to +40mV




29/70




> Reverse polarization

Na+ channels becomerefractoryCannot open againuntil resting potentialis re-established




30/70

Refractory Period




> After-hyperpolarization

Neuron overshoots restingpotential.External K+diffuses, restoringresting potentialNa+/K+pump restores ion

balance




31/70




32/70

> Propagated signal retains intensity

As action potentialis transmitted down

axon, it is constantlyrenewed- depolarization ofarea around actionpotential createsnew action potential.

Propagation of The Action Potential



33/70

> Speed of conduction varies:

Thin unmyelinated -> less than1 m/s

Thick unmyelinated -> 10m/sThick myelinated -> 100 m/sElectricity -> 300,000,000 m/s

Propagation of The Action Potential



34/70

> Action Potential jumps from one node to the next:

AP cannot regenerateat myelin due to1- insulation2- Na+ channels

mostly at nodes

Positive charges repel

to next node

AP re-established

Saltatory conduction = fast propagation of AP

Nodes of Ranvier

Myelin

Axon

Saltatory Conduction



35/70

> Interneurons:Lack axon or short axon.Depolarize or hyperpolarize in

proportion to the intensity of thestimulus.Alterations in membrane potential

decay rapidly as they areconducted.

Graded Potentials


X


36/70

Communication Between Neurons

> Charles Scott Sherrington Discovery of the Synapse- (1906) demonstrated gaps between neurons, behaviorally- studied the leg flexion reflex in a dog

- measured conduction velocity in sensory & motor neurons- measured distance of input to spinal cord- measured distance of output to muscle- pinched foot, measured delay until flexion- found delay longer than expected- reasoned gaps between neurons- called gaps synapses (after Cajal)

A

C

B

D E

40 m/sec

~15 m/sec


37/70

> Charles Scott Sherrington Discovery of the Synapse1) Reflexes are slower than conduction along an axon. Consequently,there must be some delay at synapses

2) Several weak stimuli presented at slightly different times or slightlydifferent locations produce a stronger reflex than a single stimulusdoes. Therefore, the synapses must be able to summate stimuli3) When one set of muscles is excited,another set is relaxed. Accordingly, theinput can simultaneously excite outputsat some synapses while inhibiting

outputs at other synapses

A

C

B

D E

40 m/sec

~15 m/sec



38/70


> Otto Leowi Discovery of Chemical Neurotransmission- (1921) demonstrated neurons transmit using a chemical messenger- stimulated frog vagus nerve

- transferred bath fromstimulated heart tosecond heart

- both hearts decreased rateof beating


39/70

> The Structure of Synapses- electron microscopy reveals synaptic structure

Synaptic vesiclesMitochondria

Neurotransmitters

GolgiComplex

Microtubules



40/70

> The Structure of Synapses- electron microscopy reveals synaptic structure


Microtubules

transportSynaptic vesicles

storage/release

Cisternae (golgi)recycling

neurotransmitter

Mitochondria

energy

Synaptic cleft

site of release

Postsynaptic

Membrane &Receptors

site of action ofneurotransmitter

Synaptic cleft is approx. 200 .Neurons have an average of 1000 synapses each.


41/70


> Most common types of synapses

Axodendritic

Axosomatic

Soma

AxonAxon

Dendrites

> Synapses are junctions between axon terminals and cellmembranes of other neurons


42/70


> Excitatory and Inhibitory Messages- Specific synapses provide excitatory (depolarizing) input- Other synapses provide inhibitory (hyperpolarizing) input

- Type I synapses = located primarily on shafts or spines of dendrites,round vesicles, thick presynaptic density, wide synaptic cleft, largeactive zone, excitatory input

- Type II synapses = located primarilyon soma, flattened vesicles, thinpresynaptic density, narrow synapticcleft, small active zone, inhibitory input

Type I Type II

C i i


43/70


> The Types of Receptors for Neurotransmitters- two main classes of receptors, ionotropic and metabotropic

Ionotropicreceptors:

Open a neurotransmitter-

dependent ion channelwhen a molecule ofneurotransmitter binds

This changes the localpostsynaptic membranepotential.

C i i B N


44/70


> The Types of Receptors for Neurotransmitters

Na+ channels:

Most importantexcitatory input

(EPSP)

K+ channels:

Inhibitory input

(IPSP)

Different receptors are coupled to different ion channels

The type of ion channel determines whether input is excitatory or

inhibitory

C i i B N


45/70

Ca++ channels:

Excitatory input

(EPSP)



Different receptors are coupled to different ion channels

The type of ion channel determines whether input is excitatory or

inhibitory

Cl- channels:

Decrease thedepolarization ofexcited neurons

(neutralize EPSP)

C i ti B t N


46/70



Neurons exhibit a basal rate of firing of action

potentials:

basal or spontaneous firing rate

excitatory input

inhibitory input

C i ti B t N


47/70


> The Types of Receptors for NeurotransmittersMetabotropic receptors: activate an associated protein (G protein)which triggers the opening of an ion channel.

This changes the local postsynaptic membrane potential or changes chemicalactivities within the cell.

C i ti B t N


48/70



C i ti B t N


49/70

Excitatory Postsynaptic Potential (EPSP) andInhibitory Postsynaptic Potential (IPSP)


> EPSP:

Depolarizing input to the somaor a dendrite produces a localgraded EPSP

> IPSP:

Hyperpolarizing input to the

soma or a dendrite producesa local graded EPSP

C i ti B t N


50/70

Summation of EPSPs and IPSPs


Summation of Excitatory Post Synaptic Potentials

MembranePotential(mV)

-90

-80

-70

-60

-50

-40

threshold

Summation of Inhibitory Post Synaptic Potentials

MembranePotential(mV)

-90

-80

-70

-60

-50

-40

threshold

EPSPEPSP

IPSPIPSP

C i ti B t N


51/70

Summation of EPSPs and IPSPs


> EPSPs summate to

produce an ActionPotential

> IPSPs counteract the

effects of EPSPs to blockthe Action Potential

C i ti B t N


52/70

Spatial Summation


Summation

Summation

Cancellation

excitatory

synapsesinhibitory

synapses

A

B C

D

A B

C D

A C

C i ti B t N


53/70

TemporalSummation

Communication Between Neuronsinhibitory

synapseA B

A

B

excitatory

synapse

A

B

A A

B B

No Summation

No Summation

Summation

Summation

C i ti B t N


54/70

Temporal and Spatial Summation


> EPSPs and IPSPs:

Excitatory and inhibitory inputsdiffuse along the interior surface ofthe cell membrane, summate (orcancel) and the net potential

registered at the axon hillock mayinitiate an action potential.

Comm nication Bet een Ne rons


55/70


> Axoaxonic synapses A Special Case:Axoaxonic synapses do not contribute directly to neural integration.

Rather, they modulate the amount of neurotransmitter release fromthe terminal boutons of the postsynaptic neuron.

Ordinarily the number of quanta of

neurotransmitter release per action potentialis constant.

presynaptic inhibition: decrease in neurotransmitter releasepresynaptic facilitation: increase in neurotransmitter release

due to actions of axoaxonic synapses

Axoaxonic

Other Types of Synapses



56/70


varicosities

electrical synapses

Other Types of SynapsesDendrodendritic synapses :Occur on some very small interneurons.May participate in regulatory functions

- e.g. organization of groups of neurons

small size, difficult to study, function unknown

Varicosities:

Not really synapses, beadlike swellings along

axon where neurotransmitter is releasedGap Junctions (Electrical Synapses) :

narrow gapion channels communicate directly between cells

common in invertebrates, less common invertebrates.

functions largely unknown in vertebrates- may participate in neuroadaptive processes

such as sensitization.



57/70


> Nonsynaptic Chemical Communication:Neurons have membrane-bound receptorsall over their membranes. Neurons also

have cytosolic and nuclear receptors.

These non-synaptic receptors bind avariety of specific neurotransmitters,neuromodulators, and hormones.

Most non-synaptic membrane-bound

receptors are metabotropic. Some areionotropic. All known cytosolic andnuclear receptors are metabotropic.

Other Types of Synapses



58/70

axon collateral oscillator circuit

Communication Between NeuronsTypes of Circuits

simple neural

chain

convergence and

divergence



59/70

> Seven Stages in Neurotransmitter Function-


1. Neurotransmitters are synthesized.

2. Neurotransmitters are stored in vesicles.

3. Neurotransmitters that leak fromvesicles are destroyed by enzymes.

4. Action potentials cause vesicles to fusewith membrane and releaseneurotransmitters into the synapse.

5. Released neurotransmitters bind toautoreceptors and inhibit further synthesis

and release.6. Released neurotransmitters bind to

postsynaptic receptors.

7. Released neurotransmitters are removedby reuptake or enzymatic degradation.



60/70



1. Neurotransmitters are synthesized.

Protein and peptide neurotransmitters are

synthesized from DNA template in thesoma. These proteins/peptides may bealtered after synthesis

Other neurotransmitters are synthesized bymodification of ingested substances. Thesemay be manufactured right in the axonterminal.

Energy for these actions is provided bychemical reactions in the mitochondria.



61/70



2. Neurotransmitters are stored in vesicles.

Vesicular packaging occurs in the golgiapparatus in the cell body or in the axonterminal.

Some vesicles are further packaged intostorage granules that hold many vesicles.



62/70



3. Neurotransmitters that leak fromvesicles are destroyed by enzymes.

Catabolizing enzymes (proteins) digest any

neurotransmitter molecules that leak out ofvesicles.



63/70



4. Action potentials cause vesicles to fuse

with membrane and releaseneurotransmitters into the synapse.

Action potentials actually cause vesicles tomigrate toward the presynaptic membrane

and to fuse to the membrane.



64/70

Action

Potential

docked synaptic vesiclepresynapticmembrane

proteins

calcium entryopens fusion

pore

fusionpore opens neurotransmitter release

omega figures

> Seven Stages in Neurotransmitter Function


Released neurotransmitters diffuse passively across the synapse.



65/70



5. Released neurotransmitters bind toautoreceptors and inhibit further synthesis

and release.Autoreceptors are located on the

presynaptic neuron that releases theneurotransmitter. They activatemechanisms in the neuron that inhibitfurther synthesis and release.



66/70



6. Released neurotransmitters bind topostsynaptic receptors.



67/70

> Seven Stages in Neurotransmitter Function- The released neurotransmitter binds to a specific site on apostsynaptic receptor protein.

- Depending upon which type of receptorthe neurotransmitter binds to, it will either:1) cause excitation (depolarization) of the

postsynaptic neuron, or

2) cause inhibition (hyperpolarization) of thepostsynaptic neuron, or

3) produce changes in chemical activities insideof the postsynaptic neuron

- The effect from releasing one vesicle fullof neurotransmitter on the postsynaptic neuron is very small a

quantum effect. Many quanta are required to significantly alter theactivity of the postsynaptic neuron.




68/70



7. Released neurotransmitters are removedby reuptake or enzymatic degradation.



69/70

> Seven Stages in Neurotransmitter Function


> Reuptake

> Enzymatic

Degradation

> AChE

> MAO

> transporters

2 Mechanisms

of deactivation:

Reading Assignment


70/70

Reading Assignment

Before next classChapter 4: The Chemical Basis of Behavior: Neurotransmitters

and Neuropharmacology

Rosenzweig, Breedlove, & Watson

1.2. neurophysiology-conduction, transmission, and the integration of neural signals (slide...

Documents