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The Time Machine:. Transforming Molecular Signals. into Long-Lasting Synaptic Change. David Santucci Quantitative Biology Bootcamp 2009. Presynaptic Release. Long Term Potentiation. Difference in time scale > 6 orders of magnitude. Induction. Expression. Early. Late. - PowerPoint PPT Presentation

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Presynaptic Release Long Term Potentiation

Difference in time scale > 6 orders of magnitude

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Early

Induction Expression

Late

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LTP Induction Protocols

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Blocking NMDA Receptors Blocks LTP

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Uncaging Ca2+ Alone Can Induce LTP

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Long Term Depression

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Prot

Prot

ProtK

P

P

Protein Kinases Catalyze the Phosphorylation of Proteins

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CaMKII

P

P

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Early

Induction Expression

Late

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LTP Leads to an Increase in Surface AMPA Receptors

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LTP Leads to an Increase in Spine Size

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Early

Induction Expression

Late

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Blocking Protein Synthesis Blocks the Late Phase of LTP

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LTPTAG

Prot

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Weak Stimulus Followed by a Strong Stimulus Produces LTP

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Molecular Makeup of the PSD

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Scaffolding Molecules

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PSD Proteins Are In Flux

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Actin Treadmilling, Capping, Cutting and Cross-Linking

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Actin Treadmilling, Capping, Cutting and Cross-Linking

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Single-Particle Tracking of AMPA Receptor Diffusion

AMPA

AB

QDOT

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Imaging of Isolated PSDs with Immunogold EM

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EM Tomography of Molecular-Scale Structures in the PSD

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Förster Resonance Energy Transfer (FRET)

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Super-Resolution Imaging Using FPALM

488 nm 507 nm 405 nm 555 nm 572 nm

Bleached

Dendra2

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405 nm 555 nm 572 nm488 nm 507 nm

Super-Resolution Imaging Using FPALM

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Super-Resolution Imaging Using FPALM

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