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Synaptic plasticity: Introduction

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37 diapositives · 578 Views · Oct 13, 2014

Synaptic plasticity: Introduction. Different induction protocols Basic properties Key elements of the biophysics Site of change: pre or post-synaptic More on Mechanism. Rate based induction (show on board). But: Heterosynaptic LTD – from Abraham (note – in vivo).

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  1. Synaptic plasticity: Introduction • Different induction protocols • Basic properties • Key elements of the biophysics • Site of change: pre or post-synaptic • More on Mechanism

  2. Rate based induction (show on board)

  3. But: Heterosynaptic LTD – from Abraham (note – in vivo) Christie et. Al 1995 Note about the different meanings of hetero

  4. Pairing induced plasticity Feldman, 2000 Show voltage clamp

  5. Spike timing dependent plasticity Anatomy figure from Markram 97 Markram et. al. 1997

  6. Spike timing dependent plasticity Markram et. al. 1997

  7. Bi and Poo J. Neurosci. 1998

  8. Some properties (observations) of synaptic plasticity • Synapse specificity (but) • Associatively (pre and post occur together) • Cooperativety (two different input pathways can boost each other)

  9. 1. Voltage dependence 2. Calcium permeability

  10. Some key elements of the biophysics of induction 1. NMDA receptors are necessary (in many systems) for the induction of LTP and LTD Control With APV Bi and Poo, 1998 Same hold for LTD – but some forms of plasticity are NMDAR independent

  11. Partial blockade of NMDA-R Cummings et. al , 1996

  12. 2. Calcium influx is necessary for plasticity and its level determines the sign and magnitude of plasticity

  13. And might be sufficient Yang, Tang Zucker, 1999

  14. Moderate, but prolonged calcium elevation = LTD • High calcium elevation = LTP • ( brief is sufficient, but what will long do? ) Yang, Tang Zucker, 1999

  15. Magic Magic LTP LTD High/Correlated activity Low/uncorrelated activity High NMDA-R activation Modelrate NMDA-R activation High Calcium Moderate Calcium LTP LTD

  16. What changes during synaptic plasticity? • What is the mechanism responsible for the induction of synaptic plasticity? (magic?) • Can every form of plasticity be accounted for by STDP? • What are the rules governing synaptic plasticity? • How is synaptic plasticity maintained?

  17. What can change during synaptic plasticity? • Presynaptic release probability • The number of postsynaptic receptors. • Properties of postsynaptic receptors

  18. Possible evidence for a presynaptic mechanism • Change in failure rate (minimal stimulation) • 2. Change in paired pulse ratio • (explain on board – for both ppf and ppd) • 3. The MK 801 test

  19. Evidence for postsynaptic change: • No change in failures • No change in PPR • No change in NMDA-R component • Different change for AMPA and NMDA-R currents • No change in MK-801 Are there other possible reasons for change in PPR?

  20. The story of silent synapses • Concepts • Minimal stimulation • Effect of depolarization on NMDA-R

  21. Model of synaptic plasticity

  22. Summary – up to here.

  23. 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 P R1 R1 P R2

  24. Protein Phosphorylation Non-phosphorylated Phosphorylated Phosphorylation at s831 and s845 both increase conductance but in different ways

  25. LTD- dephosphorylation at ser 845 Lee et al. 2000

  26. LTP- phosphorylation at ser 831

  27. Trafficking of Glutamate receptors constitutive and activity dependent. Activity dependent insertion and removal and its dependence on Phosphorylation

  28. Magic Magic Dephosphorylation Phosphorylation decreased conductance decreased AMPAR number Increased conductance Increased AMPAR number LTP LTD High/Correlated activity Low/uncorrelated activity High Calcium Moderate Calcium

  29. The next two topics will be: • From activity to calcium • “Magic” – from calcium to phosphorylation: the signal transduction pathways • Keep in mind, as complex as it might seem to you, it is actually much more complex. This is a cartoon version, passed through my subjective filters • (the end)

  30. Here a picture of a spine, with sources and sinks of calcium • Sources • NMDAR • VGCC • Release from internal • stores • Sinks • Diffusion • Buffers • Pumps

  31. Calcium through NMDAR

  32. For calcium channels the more precise formulation is to use the GHK equation (See Johnston and Wu pg: ) However, for simplicity we will use the simple ‘Ohmic’ formulation: jCa

  33. t » 25 ms Ca • Ligand binding kinetics – sum of two exponentials with different time constants (Carmignoto and Vicini, 1992) • Calcium Dynamics- first order ODE NMDA receptor kinetics- sum of two exponents 0.7 0.5 0.0

  34. Show calcium transients at low and high postsynatic voltage. Talks about NMDA-R as a coincidence detector

  35. A brief summary of the signal transduction pathway leading from Calcium to Phosphorylation/ Dephosphorylation Magic =