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What processes can be modelled by long-term enhancement of synaptic efficacy in the hippocampus?

Presentation on the paper Dendritic spine changes associated with hippocampal long-term synaptic plasticity by Florian Engert & Tobias Bonhoeffer. What processes can be modelled by long-term enhancement of synaptic efficacy in the hippocampus?.

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What processes can be modelled by long-term enhancement of synaptic efficacy in the hippocampus?

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  1. Presentation on the paperDendritic spine changes associated with hippocampallong-termsynaptic plasticitybyFlorian Engert&Tobias Bonhoeffer

  2. What processes can be modelled by long-term enhancement of synaptic efficacy in the hippocampus? Neuronal plasticityCircuit reorganizationMaybe learning and memory

  3. Do the changes in synaptic magnitude have any morphological reason on the subcellular level?(I.e. is there any connection between function and structure?) Let's have a closer look at some particular regions of the postsynaptic dendrite!

  4. Techniques used Local superfusion technique to concentrate on only one active synapse Two-photon imaging to "photograph" the changing dendrite with reduced phototoxic damage

  5. Results Long-term functional enhancement of synapses in area CA1 causes spine growth on the postsynaptic dendrite,which does not occur in other regions or after solely short-term magnitude changes

  6. Experimental setup • Pyramidal neuron in CA1 (Vrest<-65mV)impaled with an intracellular recording electrode& filled with the fluorescent dye calceinElectrical stimulation of the Schaffer collaterals-->EPSPs

  7. Blocking solution of 10µM Cd^2+ & 0.8µM Ca^2+ stops transmitter release • Only a small area of about 30µm diameter is spared --> superfusion spot

  8. Relevant synapses are found • Baseline synaptic transmission is recorded • LTP(depolarization + new stimuli)6 high-resolution 3-D image stacks of the postsynaptic neuron per hour

  9. Example

  10. Controls • "Off-spot" regions: one case of new spinesNMDA-receptor antagonist AP5 (50µM) --> no LTP: no new spines Unsuccessful induction of LTP(e.g. only a short potentiation, <30 min): no new spinesIn all three conditions: randomly disappearing spines

  11. ´Blind´observer • Correlation between the emergence of new spines and an increase in synaptic efficacy • Slight anticorrelation between the disappearence of spines and an increase in synaptic efficacy • (t-test)

  12. Studies only of long-lasting changesWhat about short-term LTP & LTD? • Technical difficultiesUncertainty about the spatial location of the interesting synapses--> too large region to investigateSmall and contradictive structural changes --> too large sample number---------> Big advantages of applied techniques!

  13. Alternative (not contoversial) viewChanges in spine shape influence synaptic strength(shortening and/or widening of the neck --> reduced resistance -->increased efficacy) AnswerMaybe they occur in addition to the numerical changes& below the given spatial resolution

  14. ???________Do the emerging spines contain any active synapses?AAA_______Schould be expected so in congruity with the others

  15. ???________How are the first effects of LTP to explain if the initial morphological changes detected arise no earlier than 30min after LTP induction? AAA________At first: transient changes,then: structural and permanent ones

  16. ???_____Does the disapperance of spines depend on synaptic activityor general synaptic decay(a kind of regulation of synaptic density over the lifetime)?AAA______Data support the latter alternative,but probably some functional changes depend on synaptic activity

  17. Summary • LTP in hippocampus --> new dendritic spines???____ Also new synapses (formation within an hour after the stimulus)_____???More experiments requiredFunctional --> physiological & structural changes

  18. Note added in proof • Supporting evidence from another experimental set up:Strong synaptic acticity --> new dendritic processes(M. Maletic-Savatic,R.Malinow& K.Svoboda,Science 283,1923-1927;1999)

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