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Transcript of High/Correlated activity HighCalcium LTP Low/uncorrelated activity Moderate Calcium Calcium LTD LTD...
![Page 1: High/Correlated activity HighCalcium LTP Low/uncorrelated activity Moderate Calcium Calcium LTD LTD Magic High NMDA-R activation Moderate NMDA-R activation.](https://reader030.fdocuments.in/reader030/viewer/2022032723/56649f525503460f94c76339/html5/thumbnails/1.jpg)
High/Correlated activity
High High CalciumCalcium
LTP
LTP
Low/uncorrelated activity
ModerateModerate CalciumCalcium
LTD
LTDLTD
Magic Magic
High NMDA-Ractivation
Moderate NMDA-Ractivation
![Page 2: High/Correlated activity HighCalcium LTP Low/uncorrelated activity Moderate Calcium Calcium LTD LTD Magic High NMDA-R activation Moderate NMDA-R activation.](https://reader030.fdocuments.in/reader030/viewer/2022032723/56649f525503460f94c76339/html5/thumbnails/2.jpg)
• What changes during the expression of synaptic plasticity?
• Is expression pre or post-synaptic
• What are the mechanisms leading from induction to expression
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• Presynaptic release probability
• The number of postsynaptic receptors.
• Properties of postsynaptic receptors
What can change during synaptic plasticity?
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A single mini
Induced release is multi-quantal
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Statistics of the quantal hypothesis:
•N available vesicles•Pr- prob. Of release
Binomial statistics:
K
NKNr
Kr PPNKP )1()()|(
![Page 6: High/Correlated activity HighCalcium LTP Low/uncorrelated activity Moderate Calcium Calcium LTD LTD Magic High NMDA-R activation Moderate NMDA-R activation.](https://reader030.fdocuments.in/reader030/viewer/2022032723/56649f525503460f94c76339/html5/thumbnails/6.jpg)
•N available vesicles•Pr- prob. Of release
Binomial statistics: Examples
K
NKr
Kr PPNKP )1()()|(
mean:
variance:
NPK r
)1(2rr PPN
Note – in real data, the variance is larger
![Page 7: High/Correlated activity HighCalcium LTP Low/uncorrelated activity Moderate Calcium Calcium LTD LTD Magic High NMDA-R activation Moderate NMDA-R activation.](https://reader030.fdocuments.in/reader030/viewer/2022032723/56649f525503460f94c76339/html5/thumbnails/7.jpg)
Possible evidence for a pre-synaptic mechanism
1. Change in failure rate (minimal stimulation)
Probability of failure:N vesicles, Pr – prob of release
NrPfailureP )1()(
![Page 8: High/Correlated activity HighCalcium LTP Low/uncorrelated activity Moderate Calcium Calcium LTD LTD Magic High NMDA-R activation Moderate NMDA-R activation.](https://reader030.fdocuments.in/reader030/viewer/2022032723/56649f525503460f94c76339/html5/thumbnails/8.jpg)
2. Change in coefficient of variation CV
Assume a synapse with N vesicles available for release each with a probability of release Pr and each vesicle released causes a postsynaptic response with magnitude μ.
The mean response is:
The variance is:
The CV2 (variance/mean2 ) is:
rPN
)1(2rr PPN
r
r
r
rr
PN
P
PN
PPNCV
1)1(222
22
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Plot on matlab CV2 vs Pr and vs. N:
![Page 10: High/Correlated activity HighCalcium LTP Low/uncorrelated activity Moderate Calcium Calcium LTD LTD Magic High NMDA-R activation Moderate NMDA-R activation.](https://reader030.fdocuments.in/reader030/viewer/2022032723/56649f525503460f94c76339/html5/thumbnails/10.jpg)
Short term synaptic dynamics:
depression facilitation
3. Change in paired pulse ratio (PPR)
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Synaptic depression:
• Nr- vesicles available for release.
• Pr- probability of release.• Upon a release event NrPr of the vesicles are
moved to another pool, not immediately available (Nu).
• Used vesicles are recycled back to available pool, with a time constant τu
Tru
uuirrr
NNN
NttNPdt
dN
/)(
![Page 12: High/Correlated activity HighCalcium LTP Low/uncorrelated activity Moderate Calcium Calcium LTD LTD Magic High NMDA-R activation Moderate NMDA-R activation.](https://reader030.fdocuments.in/reader030/viewer/2022032723/56649f525503460f94c76339/html5/thumbnails/12.jpg)
urTirrr NNttNP
dt
dN /)()(
Therefore:
And for many AP’s:
urTii
rrr NNttNP
dt
dN /)()(
NuNr
1/τu
![Page 13: High/Correlated activity HighCalcium LTP Low/uncorrelated activity Moderate Calcium Calcium LTD LTD Magic High NMDA-R activation Moderate NMDA-R activation.](https://reader030.fdocuments.in/reader030/viewer/2022032723/56649f525503460f94c76339/html5/thumbnails/13.jpg)
Show examples of short term depression.
How might facilitation work?
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urTii
rrr NNttNP
dt
dN /)()(
NuNr
1/τu
Are there other possible reasons for change in PPR?
Postsynapticspine
![Page 15: High/Correlated activity HighCalcium LTP Low/uncorrelated activity Moderate Calcium Calcium LTD LTD Magic High NMDA-R activation Moderate NMDA-R activation.](https://reader030.fdocuments.in/reader030/viewer/2022032723/56649f525503460f94c76339/html5/thumbnails/15.jpg)
4. Open channel blocker MK-801
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Evidence for postsynaptic change:
1.No change in failures2.No change in CV3.No change in PPR4.No change in MK-801
5.Change in the magnitude of successful transmission6.No change in NMDA-R component
![Page 17: High/Correlated activity HighCalcium LTP Low/uncorrelated activity Moderate Calcium Calcium LTD LTD Magic High NMDA-R activation Moderate NMDA-R activation.](https://reader030.fdocuments.in/reader030/viewer/2022032723/56649f525503460f94c76339/html5/thumbnails/17.jpg)
The story of silent synapses
before after
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The story of silent synapses
Concepts• Minimal stimulation• Effect of depolarization on NMDA-R
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Model of synaptic plasticity
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Mechanisms for the induction of synaptic plasticity
• Phosphorylation of receptors
• Phosphatases, Kinases and Calcium
• How do we model the Phosphorylation cycle
• Receptor trafficking
• Receptor trafficking and Phosphorylation
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Phosphorylation state of Gultamate receptors is correlated with LTP and LTD
GluR1-4, functional units are heteromers, probably composed of 4 subunits, probably composes of different subtypes.
Many are composed of GluR1 and GluR2
R2
R2
R1 P
P
R1
![Page 23: High/Correlated activity HighCalcium LTP Low/uncorrelated activity Moderate Calcium Calcium LTD LTD Magic High NMDA-R activation Moderate NMDA-R activation.](https://reader030.fdocuments.in/reader030/viewer/2022032723/56649f525503460f94c76339/html5/thumbnails/23.jpg)
Protein Phosphorylation
Non-phosphorylated Phosphorylated
Phosphorylation at s831 and s845 both increase conductance but in different ways
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LTD- dephosphorylation at ser 845
Lee et al. 2000
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LTP- phosphorylation at ser 831
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Trafficking of Glutamate receptors constitutive and activity dependent.
Activity dependent insertion and removal and its dependence on Phosphorylation
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Malinow, Malenka 2002
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There are two trafficking pathways:
1- Short, in which there is constant plasticity independent trafficking. But dephosphorylation at ser 880 on GluR2 might still trigger LTD.
2- Long, in which phosphorylation triggers LTP.
Note – Phosphorylation also increases conductance directly
![Page 30: High/Correlated activity HighCalcium LTP Low/uncorrelated activity Moderate Calcium Calcium LTD LTD Magic High NMDA-R activation Moderate NMDA-R activation.](https://reader030.fdocuments.in/reader030/viewer/2022032723/56649f525503460f94c76339/html5/thumbnails/30.jpg)
High/Correlated activity
High High CalciumCalcium
LTP
PhosphorylationPhosphorylation
Increasedconductance
Increased AMPAR number
Low/uncorrelated activity
ModerateModerate CalciumCalcium
LTD
Dephosphorylation
decreaseddecreasedconductanceconductance
decreased decreased AMPAR numberAMPAR number
Magic Magic