lec 2b structure and function of cellspages.ucsd.edu › ~mboyle › cogs17 › pdf-files ›...

Lec 2bStructureandFunctionofCells

Cogs17CognitiveNeuroscienceUCSD

THESYNAPSE– Communicationbetweencells

ExocytosisVESICLEDoublelipidmembrane

NTs

Exocytosis

3 4 52

1Energy-RequiringProcess

VESICLEDoublelipidmembrane

NTs

Exocytosis

32

19

AftertheNThas

46

5

AftertheNTshavedriftedintothecleft...

Reclaimedemptyvesicletobere-filled

withNTs

78

Energy-RequiringProcess

Functionsofvariousproteins embeddedinneuronmembranes:

IonGatesFusionPoresReceptorSites

Eachisspecializedforonlyonefunction

TheSynapse

DoubleLipidMembranes

SynapticCleft

FusionPore(releasingNT)

GABA

ReceptorSites

TheSynapse

GABA

NTisreleasedintoSynapticCleftwhereitfloatsaround

untilitchancestobumpagainstaReceptorSitethatitfits

TheSynapse

ACh

Na+

Cl-

K+

CA++

Glia

Enzyme

Whathappensnextdependson...

TheSynapse

AChNa+

Cl-

K+

CA++

Glia

Enzyme

WhenNTattachestoReceptorsite,

>>Iongateopens

Cl-ExcitatoryPost-SynapticPotential

Post-synapticcellisHYPO-Polarized

TheSynapse

ACh

Na+

AddingpositivelychargedNa+decreasespolarityofpost-synapticcell,bringingitclosertoitsthresholdforfiring

=Excitation

Hypo- (less)polarization

TheSynapse

GABA

Cl-

Na+

K+

CA++

Glia

Enzyme

Na+

TheSynapse

Cl-

AddingnegativelychargedCl-increasespolarityofpost-synapticcell,

pushingitfartherfromitsthresholdforfiring=Inhibition

"IPSP"InhibitoryPost-SynapticPotential

Post-synapticcellisHYPER-Polarized

GABA

Hyper- (more)polarization

Summation

Multipleexcitatoryandinhibitoryinputsconverge

oneachcell

MNEMONIC:EPSP&IPSP

• EPSP=Excitatory Post-SynapticPotential

• CellisHYPO-Polarized

• Whenyouareexcited,yousay“O!”

• IPSP=Inhibitory Post-SynapticPotential

• CellisHYPER-Polarized• Whenyouareinhibited,yousay“ER...”

Na+

AFTER theSynapse...

Cl-

GABA

K+

CA++

Glia

Enzyme

Na+

AFTER theSynapse...

Cl-

NT

K+Glia

Enzyme CA++

IonGatecloses,NTdetaches

Na+

AFTER theSynapse...

Cl-

K+

NTGlia

Enzyme CA++

Astro-GliamaycarryNToff,

disposeintobloodstream

Na+

AFTER theSynapse...

Cl-

K+

NT

Enzyme CA++

Glia

Na+

AFTER theSynapse...

Cl-

K+

NT

CA++

Glia

EnzymemaydeactivateNT

Enzyme

Na+

AFTER theSynapse...

Cl-

K+

CA++

Glia

EnzymemaydeactivateNT

TNABA

Enzyme

Na+

AFTER theSynapse...

Cl-

K+

NT

Enzyme CA++

Glia

Na+

AFTER theSynapse...

Cl-

K+

NT

Enzyme CA++

Glia

PreSynapticCellmayRe-Uptake NT

Na+

Cl-

K+

Enzyme CA++

Glia

PreSynapticCellmayRe-Uptake NT

NT

AFTER theSynapse...

Neurotransmitter

Bindstothepost,butdoesn’tgoin,floatsbackhometobeusedagain.

MNEMONIC

Ionotrophic Synapse

ACh

Cl-

K+

CA++

Glia

Enzyme

WhenNTattachestoReceptorsite,

>>Iongateopens

Na+

Na+

Cl-K+

EnzymeCA++

Glia

Metabotrophic Synapse

5HT

Post-SynapticCell Ribosomes(formanufacturingproteins)

Na+

Cl-K+

EnzymeCA++

Glia


5HT

Post-SynapticCell

NTattaches,Receptorsitechangesitconfigurationinside Post-synapticcell

Releasesa"GProtein"

Ribosomes(formanufacturingproteins)

G

Na+

Cl-K+

EnzymeCA++

Glia


5HT


G 2nd

PresenceofG-Proteinstriggersproductionof"SecondMessengers"

Na+

Cl-K+

EnzymeCA++

Glia


5HT


G 2nd

PresenceofG-Proteinstriggersproductionof"SecondMessengers"

SecondMessengerbindsw/G-Protein

Na+

Cl-K+

EnzymeCA++

Glia


5HT


Thiscomplexthenopensa

separate IonGatefrominsidecell.

G 2nd

Na+

Cl-K+

EnzymeCA++

Glia


5HT


Thiscomplexthenopensa

separate IonGatefrominsidethecell.

G 2nd

Ionotrophicvs.Metabotrophic

• Rapidresponse• Veryshort-lived• Forsendingmessage

alongapathway

• Slowresponse• Longlasting• Forsettingconditions

(e.g.mood,attention)

Neurotransmitters

• Acetylcholine(ACh)• GABA• Glutamate• Serotonin(5HT)• Dopamine• Norepinephrine• Epinephrine(Adrenalin)• SubstanceP• Endorphins• Hormones

• Allneuro-muscularjunctions;Corticalarousal...

• Suppresscorticalactivity;Regulateanxiety...

• Mostcommon+;Learning,Perception,Schiz...

• Oftenaneuromodulator;Mood,Sleep,Percep...

• Reinforcement;Atten;Motorcontrol (Parkinsons)...

• Arousal;Attention...

• Arousal;Attention...

• Pain(damage,itch,extremetemp,etc)

• CountereffectsofSubstanceP

• e.g.Testosterone,Estrogen,Oxytocin,Insulin,CCK,Cortisol,Adrenalin,...

SOMEFUNTIONS:SOMENTs:

Agonistsvs.Antagonists

AGONIST

• Increases thelikelihoodofaNeurotransmitterhavingitseffect(+or-)

ANTAGONIST

• Decreases thelikelihoodofaNeurotransmitterhavingitseffect(+or-)

GABA GABA

Na+

Cl-K+

CA++

ACh

AChE

Glia

WhatworksasanAgonist vs.AntagonistoftendependsonhowNT

istypicallyprocessedinthecleftPre-SynapticCell

Post-SynapticCell

Acetylcholine(ACh)intheCleftAgonistsvs.Antagonists

Na+

Cl-K+

CA++Glia

AChAChE

WhenAChdetachesfromReceptorSiteintocleft...



Post-SynapticCell


Na+

Cl-K+

CA++Glia

AChAChEAcetylcholine-Esterase,

anEnzymeincleft,willbreakdownACh



Post-SynapticCell


Na+

Cl-K+

CA++Glia

Acetylcholine-Esterase,anEnzymeincleft,willbreakdownACh

...intoAcetateandCholineACh

AChE ACh



Post-SynapticCell


Na+

Cl-K+

CA++

GliacellscarryoffAcetate,

todisposeinbloodstream

ACh

AChE

Glia

ACh



Post-SynapticCell


Na+

Cl-K+

CA++

GliacellscarryoffAcetate,

todisposeinbloodstreamAChE

AChGlia

ACh



Post-SynapticCell


Na+

Cl-K+

CA++

Re-Uptake

AChE ACh

Pre-SynapticCell

Post-SynapticCell


Na+

Cl-K+

CA++

Re-Uptake

AChETheCholineisre-uptakenintothe

Pre-Synapticcellforre-use

ACh

Pre-SynapticCell

Post-SynapticCell


Na+

Cl-K+

CA++

Re-Uptake

AChETheCholineisre-uptakenintothe

Pre-Synapticcellforre-use

ACh


Pre-SynapticCell

Post-SynapticCell

Na+

Cl-K+

CA++

AChAChE-BlockerAChE

AnAChE-BlockerisanAChAgonist

Pre-SynapticCell

Post-SynapticCell


Na+

Cl-K+

CA++

ACh

AChE-Blocker

AChE

Bypreventingthebreak-downofACh,theAChE-BlockerfreesACh

tore-stimulatethePost-Syntaticcell


Pre-SynapticCell

Post-SynapticCell


Na+

Cl-K+

CA++

ACh


AChE-Blocker

AChE

Bypreventingthebreak-downofACh,theAChE-BlockerfreesACh

tore-stimulatethePost-Syntaticcell

Pre-SynapticCell

Post-SynapticCell


Na+

Cl-K+

CA++

AChAChE

AChGlia

AnReuptake-BlockerisanAChAntagonist

Pre-SynapticCell

Post-SynapticCell


Na+

Cl-K+

CA++

AChAChE

AChGlia

AnReuptake-BlockerisanAChAntagonist

CholinealonecannotstimulatePost-Synapticcell,

soeffectivenessofAChreduced

Pre-SynapticCell

Post-SynapticCell


Na+

Cl-

K+CA++

5HT

Serotonin(5HT)intheCleftAgonistsvs.Antagonists

Glia

Thetypicalpatternfor5HTinthecleftisdifferent

fromthatofACh

Re-Uptake

Enzyme

Pre-SynapticCell

Post-SynapticCell

Na+

Cl-

K+CA++

Glia 5HT


5HTisre-uptakenwhole.


fromthatofACh

Re-Uptake

Enzyme

Pre-SynapticCell

Post-SynapticCell

Na+

Cl-

K+CA++

Glia

Re-Uptake

5HT


5HTisre-uptakenwhole.


fromthatofAChEnzyme

Pre-SynapticCell

Post-SynapticCell

Na+

Cl-

K+CA++

Glia 5HT


Re-Uptake

Enzyme

Pre-SynapticCell

Post-SynapticCell

So,unlike inACh,since5HTis

re-uptaken whole...

Na+

Cl-

K+CA++

Glia 5HT


...aRe-UptakeBlocker,likePROSAC,will,inthiscase,

free5HTtore-stimulatepost-synapticcell


re-uptaken whole...

Re-Uptake

Enzyme

Prosac

Pre-SynapticCell

Post-SynapticCell

Na+

Cl-

K+CA++

Glia 5HT

Re-Uptake

Enzyme

Prosac


Pre-SynapticCell

Post-SynapticCell

...aRe-UptakeBlocker,likePROSAC,will,inthiscase,

free5HTtore-stimulatepost-synapticcell


re-uptaken whole...

Na+

Cl-

K+CA++

Glia

5HT

Re-Uptake

Enzyme

Prosac


Pre-SynapticCell

Post-SynapticCell

So,unlikew/ACh,thisRe-UptakeBlockerisa5HT

Agonist

OtherFactorsthatModifyFunction

DNA

RNA

CopiesofsegmentsofDNA(=RNA)

aremade,tocodeforproteinproduction

GENETRANSCRIPTION

Dendritization– Increase#ofdendriticspines

AvailabilityofNTComponents

viaDIET...e.g.Choline

(formakingACh)frommilkornuts&seeds

e.g.Tryptophan(formaking5HT)

fromturkey

viaadministeringDRUGS...

e.g.L-DOPA(aDopamineprecursor)thatcrossesblood-brainbarrier

e.g.Fat-solubledrugs(heroin,canobinol,LSD)crossbarrierandmimicNTs

KinesinMoleculestransportingNTtoTerminal

Auto-ReceptorEXCEPTIONS

Incellswith"Auto-Receptors"

thepresynapticcellinhibitsitself,

aswellasthepost-synapticcell

(i.e.LimitshowmuchNTpresym willrelease)

InhibitoryNeurotransmitter

Axo-AxonalSynapsesEXCEPTIONS

Inbrain,activityalongPainpathways

provokesactivityfromEndorphincells.

ReceptorsitesonTerminal ofpaincellrespondstoendorphins,reducingreleaseof

SubstanceP

lec 2b structure and function of cellspages.ucsd.edu › ~mboyle › cogs17 › pdf-files ›...

Documents