1 / 23

THE AUSTRALIAN NATIONAL UNIVERSITY

THE AUSTRALIAN NATIONAL UNIVERSITY. Short-Term Synaptic Plasticity I Christian Stricker ANUMS /JCSMR - ANU Christian.Stricker@anu.edu.au http://stricker.jcsmr.anu.edu.au /STP1.pptx. Aims. The students should know forms of short-term plasticity (STP) ;

makaio
Télécharger la présentation

THE AUSTRALIAN NATIONAL UNIVERSITY

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. THE AUSTRALIAN NATIONAL UNIVERSITY Short-Term Synaptic Plasticity IChristian StrickerANUMS/JCSMR - ANUChristian.Stricker@anu.edu.auhttp://stricker.jcsmr.anu.edu.au/STP1.pptx

  2. Aims The students should • know forms of short-term plasticity (STP); • recognise how synaptic efficacy is quantified; • understand the time, over which STP occurs; • be familiar with the 3 phases of plasticity; • appreciate that STP is mostly presynaptic; • be aware of what causes facilitation; • have an understanding of Ca2+sources and extrusion mechanisms; and • appreciate the dynamics involved in STP.

  3. Contents • Defining relevant terms • Different forms of plasticity • Phases: induction, expression, maintenance • Quantifying changes in plasticity: pre- and postsynaptic mechanisms… • Possibilities to alter synaptic efficacy • Facilitation: more than residual Ca2+ • Ca2+ homeostasis in nerve terminals • Sequences in STP: induction and their relief

  4. Synaptic Plasticity • Activity-dependent change in synaptic efficacy • Dependent on previous history of synaptic stimulation • Many different histories of synaptic stimulation • One pulse, two pulses (paired-pulse), multiple pulses, etc. • Different frequencies: slow rate (5 Hz), tetanus (100 Hz), etc. • Forms • Efficacy: • Increase in synaptic efficacy: Potentiation • Other notions used: facilitation, augmentation, habituation • Decrease in synaptic efficacy: Depression • Mostly no other wording used • Timing • Short-term (STP): ms - min (<h) • Long-term: h - d - y(?)

  5. Examples of Plasticity • Form of plasticity is specific to type of synapse (pre- and postsynaptic) and induction protocol. • Purely descriptive - does not imply molecular mechanisms. • Time course of plasticity may provide some clues as to mechanisms. • Different stimuli induce different forms of plasticity.

  6. ThreePhases ofSynapticPlasticity • Induction: Where at the synapse is the change in efficacy STARTED? • Mostly via a Ca2+ influx. • Expression: What are the molecular targets that CAUSE these changes at synapse? • Maintenance: What KEEPSchange in efficacy UP? Of little interest in short-term plasticity (STP) but important in LTP (see later).

  7. Quantifying Synaptic Plasticity • EPSC = npQ • Number of release sites: nPresynaptic • Probability: pPresynaptic • Quantal size: QPostsynaptic • How can efficacy be changed? • n, p, and Q(all of them…) • Increase = potentiation • Decrease = depression

  8. How Could Changes Occur? • Quantal size: Q • Insertion/retrieval of receptors • Unmasking of receptors • Alterations in receptor response • Number of release sites: n • Unmasking of “silent” sites • Unlikely very fast • Probability: p • Excitability of membrane • De-/hyperpolarisation via Na+& K+ channels, etc. • Vesicle availability • Reuptake • Repriming • Ca2+ availability • Action potential shape • Ca2+ channels • Ca2+ handling

  9. Short-Term Plasticity (STP) • All forms share ONE feature, namely that, in general, quantal content (n * p) changes, but not quantal size (Q). • There is a high correlation between changes in n and p. • Conclusion: MOSTLY presynaptic.

  10. Different Forms of STP • Facilitation • Induced by SINGLE action potentials (APs) • Lasts typically a few 10s of ms • Augmentation • Induced by a lot of APs (100 at ~10 Hz) • Lasts typically a few s • Post-tetanicpotentiation (PTP) • Induced by a series of APs (>50 Hz) for several s • Lasts typically a few 10s ofs • Forms can coexist - experimentally often difficult to separate.

  11. Facilitation • Subsequent stimuli result in larger EPSPs. • Often quantified as (here ~ 2x). • Increase for 3rd is bigger than for 2nd. Rozov et al. (2001), J Physiol 531: 807-826.

  12. Calcium and Facilitation • P→B synapse shows strong facilitation. • EGTA as a Ca2+chelator abolishes facilitation: • Facilitation caused by Ca2+ • Ca2+ sensor has lower affinity than that for release: • Ca2+ binds to something other than synaptotagmin to cause facilitation. • Residual Ca2+ hypothesis: • Ca2+ sources • Ca2+ extrusion mechanisms Rozov et al. (2001), J Physiol 531: 807-826.

  13. Ca2+ Sourcing in Terminals • Ca2+channels • VDCC: N, P, Q, R, T, L • TRPC (?) • CRAC (Orai/ STIM1 ?) • Ligand gated channels (ionotropicautoreceptors) • NMDA receptors • AMPA receptors (GluR2-def.) • ACh receptors • Ca2+stores / organelles • SER • IP3 receptors • Ryanodine receptors • Mitochondria • Transporter (Vm!) • NCX: 3 Na+ / 1 Ca2+

  14. Ca2+ Sequestration in Terminals • into extracellular space • Ca2+-ATPase (base load) • Na+/Ca2+ exchanger • into intracellular volume • Organelles: • SERCA pump (SER) • Ψ-uniporter (mitochondria) • Buffers (temporary; cal-pain, calmodulin, etc): • Fixed buffers (fixed proteins - cytoskeleton, membrane bound) • Mobile buffers (soluble proteins, acids, etc.)

  15. Mechanisms of Facilitation • Central is a low p • unlikely release on first AP • depletion not important • Repeated stimulation causes Na+ and Ca2+ load. • Na+/Ca2+-exchanger increases Ca2+→ [Ca2+]res↑: • does not explain total amount of facilitation. • Additional vesicle priming, etc. required. Modified from Zucker (1989), Annu Rev Neurosci 12: 13-31.

  16. Nonlinear Ca2+-Dependence • Ca2+-cooperativity: ≥ 4 Ca2+ bind to release machinery: 4 Ca2+ + X ⇌ XCa2+4 • Numeric example: • Facilitation: 2-fold (100%) • Ca2+ increase: ~5 µM • Ca2+ for release: ~380 µM • Residual Ca2+ cannot account for total facilitation. Dodge & Rahamimoff (1967), J Physiol 193: 419-432.

  17. Ca2+ and Vesicle Mobilisation • One idea - not the only one… • Not all vesicles are free to move: • Some are fixed to actin via synapsin1. • Ca2+-dependent mobilisationof “fixed” vesicles. • Increased vesicle availability. ∴ Idea yet to be tested (difficult…). Walmsley et al. (1998), TINS 21: 81-88.

  18. Mechanisms Causing Facilitation • All phases in presynaptic nerve terminal. • Induction: • [Na+] ↑ → [Ca2+]res↑ • Expression • Non-linear Ca2+ dependence (small) • Ca2+-dependent vesicle mobilisation • Maintenance • Determined by Ca2+ extrusion.

  19. Sequences in STP • Low p hippocampal synapses: small release → facilitation. • Tetanus >50Hz for 12s • Facilitation: fast, initial • Augmentation: slower • Depression: slowest • tbuild-up ≠ trecovery • Contribution of each form relieved during recovery. • Hierarchy of different plasticities: Facilitation →augmentation →depression and vice versa.

  20. Take-Home Messages • Short-term plasticity takes from 10 ms - few min. • Different forms can coexist at a synapse. • Facilitation is associated with low p. • Multiple mechanisms exist to homeostati-cally regulate Ca2+ in nerve terminals. • Mechanisms for facilitation not only include [Ca2+]res but also vesicle priming.

  21. References • Textbooks • Byrne & Roberts “From Molecules to Networks”(2004), pp. 235ff • Kandel et al. (4th ed.), 1247-1254 • Reviews • Zucker RS, Regehr WG (2002) Short-Term Synaptic Plasticity. Ann. Rev. Physiol. 64: 355-405. • Fortune ES, Rose GJ (2001) Short-Term Synaptic Plasticity as a Temporal Filter. Trends Neurosci. 24: 381-385.

  22. That’s it folks…

More Related