lec 2b structure and function of cellsmboyle/cogs17/pdf-files/su... · excitatory post-synaptic...
Post on 08-Nov-2020
6 Views
Preview:
TRANSCRIPT
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
Metabotrophic Synapse
5HT
Post-SynapticCell
NTattaches,Receptorsitechangesitconfigurationinside Post-synapticcell
Releasesa"GProtein"
Ribosomes(formanufacturingproteins)
G
Na+
Cl-K+
EnzymeCA++
Glia
Metabotrophic Synapse
5HT
Post-SynapticCell Ribosomes(formanufacturingproteins)
G 2nd
PresenceofG-Proteinstriggersproductionof"SecondMessengers"
Na+
Cl-K+
EnzymeCA++
Glia
Metabotrophic Synapse
5HT
Post-SynapticCell Ribosomes(formanufacturingproteins)
G 2nd
PresenceofG-Proteinstriggersproductionof"SecondMessengers"
SecondMessengerbindsw/G-Protein
Na+
Cl-K+
EnzymeCA++
Glia
Metabotrophic Synapse
5HT
Post-SynapticCell Ribosomes(formanufacturingproteins)
Thiscomplexthenopensa
separate IonGatefrominsidecell.
G 2nd
Na+
Cl-K+
EnzymeCA++
Glia
Metabotrophic Synapse
5HT
Post-SynapticCell Ribosomes(formanufacturingproteins)
Thiscomplexthenopensa
separate IonGatefrominsidethecell.
G 2nd
Na+
Cl-K+
EnzymeCA++
Glia
Metabotrophic Synapse
5HT
Post-SynapticCell Ribosomes(formanufacturingproteins)
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...
WhatworksasanAgonist vs.AntagonistoftendependsonhowNT
istypicallyprocessedinthecleftPre-SynapticCell
Post-SynapticCell
Acetylcholine(ACh)intheCleftAgonistsvs.Antagonists
Na+
Cl-K+
CA++Glia
AChAChEAcetylcholine-Esterase,
anEnzymeincleft,willbreakdownACh
WhatworksasanAgonist vs.AntagonistoftendependsonhowNT
istypicallyprocessedinthecleftPre-SynapticCell
Post-SynapticCell
Acetylcholine(ACh)intheCleftAgonistsvs.Antagonists
Na+
Cl-K+
CA++Glia
Acetylcholine-Esterase,anEnzymeincleft,willbreakdownACh
...intoAcetateandCholineACh
AChE ACh
WhatworksasanAgonist vs.AntagonistoftendependsonhowNT
istypicallyprocessedinthecleftPre-SynapticCell
Post-SynapticCell
Acetylcholine(ACh)intheCleftAgonistsvs.Antagonists
Na+
Cl-K+
CA++
GliacellscarryoffAcetate,
todisposeinbloodstream
ACh
AChE
Glia
ACh
WhatworksasanAgonist vs.AntagonistoftendependsonhowNT
istypicallyprocessedinthecleftPre-SynapticCell
Post-SynapticCell
Acetylcholine(ACh)intheCleftAgonistsvs.Antagonists
Na+
Cl-K+
CA++
GliacellscarryoffAcetate,
todisposeinbloodstreamAChE
AChGlia
ACh
WhatworksasanAgonist vs.AntagonistoftendependsonhowNT
istypicallyprocessedinthecleftPre-SynapticCell
Post-SynapticCell
Acetylcholine(ACh)intheCleftAgonistsvs.Antagonists
Na+
Cl-K+
CA++
Re-Uptake
AChE ACh
Pre-SynapticCell
Post-SynapticCell
Acetylcholine(ACh)intheCleftAgonistsvs.Antagonists
Na+
Cl-K+
CA++
Re-Uptake
AChETheCholineisre-uptakenintothe
Pre-Synapticcellforre-use
ACh
Pre-SynapticCell
Post-SynapticCell
Acetylcholine(ACh)intheCleftAgonistsvs.Antagonists
Na+
Cl-K+
CA++
Re-Uptake
AChETheCholineisre-uptakenintothe
Pre-Synapticcellforre-use
ACh
Acetylcholine(ACh)intheCleftAgonistsvs.Antagonists
Pre-SynapticCell
Post-SynapticCell
Na+
Cl-K+
CA++
AChAChE-BlockerAChE
AnAChE-BlockerisanAChAgonist
Pre-SynapticCell
Post-SynapticCell
Acetylcholine(ACh)intheCleftAgonistsvs.Antagonists
Na+
Cl-K+
CA++
ACh
AChE-Blocker
AChE
Bypreventingthebreak-downofACh,theAChE-BlockerfreesACh
tore-stimulatethePost-Syntaticcell
AnAChE-BlockerisanAChAgonist
Pre-SynapticCell
Post-SynapticCell
Acetylcholine(ACh)intheCleftAgonistsvs.Antagonists
Na+
Cl-K+
CA++
ACh
AnAChE-BlockerisanAChAgonist
AChE-Blocker
AChE
Bypreventingthebreak-downofACh,theAChE-BlockerfreesACh
tore-stimulatethePost-Syntaticcell
Pre-SynapticCell
Post-SynapticCell
Acetylcholine(ACh)intheCleftAgonistsvs.Antagonists
Na+
Cl-K+
CA++
AChAChE
AChGlia
AnReuptake-BlockerisanAChAntagonist
Pre-SynapticCell
Post-SynapticCell
Acetylcholine(ACh)intheCleftAgonistsvs.Antagonists
Na+
Cl-K+
CA++
AChAChE
AChGlia
AnReuptake-BlockerisanAChAntagonist
CholinealonecannotstimulatePost-Synapticcell,
soeffectivenessofAChreduced
Pre-SynapticCell
Post-SynapticCell
Acetylcholine(ACh)intheCleftAgonistsvs.Antagonists
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
Serotonin(5HT)intheCleftAgonistsvs.Antagonists
5HTisre-uptakenwhole.
Thetypicalpatternfor5HTinthecleftisdifferent
fromthatofACh
Re-Uptake
Enzyme
Pre-SynapticCell
Post-SynapticCell
Na+
Cl-
K+CA++
Glia
Re-Uptake
5HT
Serotonin(5HT)intheCleftAgonistsvs.Antagonists
5HTisre-uptakenwhole.
Thetypicalpatternfor5HTinthecleftisdifferent
fromthatofAChEnzyme
Pre-SynapticCell
Post-SynapticCell
Na+
Cl-
K+CA++
Glia 5HT
Serotonin(5HT)intheCleftAgonistsvs.Antagonists
Re-Uptake
Enzyme
Pre-SynapticCell
Post-SynapticCell
So,unlike inACh,since5HTis
re-uptaken whole...
Na+
Cl-
K+CA++
Glia 5HT
Serotonin(5HT)intheCleftAgonistsvs.Antagonists
...aRe-UptakeBlocker,likePROSAC,will,inthiscase,
free5HTtore-stimulatepost-synapticcell
So,unlike inACh,since5HTis
re-uptaken whole...
Re-Uptake
Enzyme
Prosac
Pre-SynapticCell
Post-SynapticCell
Na+
Cl-
K+CA++
Glia 5HT
Re-Uptake
Enzyme
Prosac
Serotonin(5HT)intheCleftAgonistsvs.Antagonists
Pre-SynapticCell
Post-SynapticCell
...aRe-UptakeBlocker,likePROSAC,will,inthiscase,
free5HTtore-stimulatepost-synapticcell
So,unlike inACh,since5HTis
re-uptaken whole...
Na+
Cl-
K+CA++
Glia
5HT
Re-Uptake
Enzyme
Prosac
Serotonin(5HT)intheCleftAgonistsvs.Antagonists
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
top related