What processes can be modelled by long-term enhancement of synaptic efficacy in the hippocampus?
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Transcript of What processes can be modelled by long-term enhancement of synaptic efficacy in the hippocampus?
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Presentation on the paper
Dendritic spine changes associated with
hippocampallong-term
synaptic plasticity
by
Florian Engert&
Tobias Bonhoeffer
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What processes can be modelled by long-term enhancement of synaptic efficacy in the
hippocampus?
Neuronal plasticityCircuit reorganizationMaybe learning and memory
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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!
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Techniques used
Local superfusion technique to concentrate on only one active synapse
Two-photon imaging to "photograph" the changing dendrite with reduced phototoxic damage
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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
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Experimental setup
• Pyramidal neuron in CA1 (Vrest<-65mV)impaled with an intracellular recording electrode& filled with the fluorescent dye calcein
Electrical stimulation of the Schaffer collaterals-->EPSPs
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• 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
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• 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
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Example
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New <-->disappearing
spinesActive <-->"off-spot"
regions
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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
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• ´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)
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Studies only of long-lasting changes
What 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!
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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
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???________Do the emerging spines contain any active synapses?
AAA_______Schould be expected so in congruity with the others
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???________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
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???_____Does the disapperance of spines depend on synaptic activity
or 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
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Summary
• LTP in hippocampus --> new dendritic spines???____ Also new synapses (formation within an hour after the stimulus)_____???More experiments requiredFunctional --> physiological & structural changes
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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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