The fate of hippocampal synapses depends on the sequence of plasticity-inducing events

  1. J Simon Wiegert
  2. Mauro Pulin
  3. Christine Elizabeth Gee
  4. Thomas G Oertner  Is a corresponding author
  1. University Medical Center Hamburg-Eppendorf, Germany
5 figures, 1 table and 1 additional file

Figures

Figure 1 with 2 supplements
with two supplements: Channelrhodopsin-driven theta-frequency stimulation induces LTP.

(A) Left: A fiber-coupled LED (λ = 470 nm) was used to locally stimulate ChR2-expressing CA3 neurons. Spines on GCaMP6s/mCerulean-expressing CA1 pyramidal cells were imaged with two-photon …

https://doi.org/10.7554/eLife.39151.002
Figure 1—figure supplement 1
Examples of optogenetic TFS experiments.

(A) Experiment where no dendritic calcium spikes were observed in the GCaMP6s-expressing CA1 pyramidal cell (colored traces, top) and no complex spike bursts (CSBs) were triggered in the neighboring …

https://doi.org/10.7554/eLife.39151.003
Figure 1—figure supplement 2
Analysis of imaging and electrophysiology data.

(A) EPSCaT amplitude of spine one is plotted for all trials shown in Figure 1B. Open circles show failures, filled circles show successes. Baseline responses (‘pre oTFS’) and responses immediately …

https://doi.org/10.7554/eLife.39151.004
Figure 2 with 2 supplements
with two supplements: Characterization of oTFS-induced LTP.

(A) Changes in excitatory postsynaptic current (EPSC) amplitude in reporter neurons immediately after and 30 min after oTFS in the absence (left) or presence (right) of the NMDA receptor antagonist …

https://doi.org/10.7554/eLife.39151.005
Figure 2—source data 1

Theta-frequency stimulation experiments.

https://doi.org/10.7554/eLife.39151.008
Figure 2—figure supplement 1
Analysis of oTFS experiments where no dendritic calcium spikes were observed during the induction protocol.

(A) The null hypothesis, no change in average EPSCaT amplitude after oTFS, could not be rejected (p>0.05, n = 17). (B) The null hypothesis, no change in EPSCaT potency after oTFS, could not be …

https://doi.org/10.7554/eLife.39151.006
Figure 2—figure supplement 2
Analysis of control experiments where no oTFS was applied to responding spines.

(A) The null hypothesis, no change in average EPSCaT amplitude over time, could not be rejected (p>0.05, n = 16). (B) The null hypothesis, no change in EPSCaT potency over time, could not be …

https://doi.org/10.7554/eLife.39151.007
Long-term outcome of oTFS-induced LTP.

(A) Analysis of volume changes of oTFS spines 30 min and 24 hr after oTFS. The volume increase 30 min after oTFS (p=0.03, n = 15 slice cultures) was not maintained 24 hr later (p=0.42). (B) Analysis …

https://doi.org/10.7554/eLife.39151.009
Figure 3—source data 1

Theta-frequency stimulation: Spine volume changes.

https://doi.org/10.7554/eLife.39151.010
Figure 4 with 1 supplement
with one supplement: LTD-induced spine elimination is reversed by LTP or sustained synaptic transmission.

(A) Long-term survival analysis after LTD. Spines were imaged at d0, d1 and d7. Below: Maximum intensity projections of mCerulean fluorescence in dendritic segment harboring a responding spine that …

https://doi.org/10.7554/eLife.39151.011
Figure 4—source data 1

Low-frequency stimulation followed by theta-freuquency stimulation.

https://doi.org/10.7554/eLife.39151.013
Figure 4—figure supplement 1
LTD followed by LTP.

(A) Outcome of all experiments where optogenetic low-frequency stimulation (oLFS) on day 0 was followed by optogenetic theta-frequency stimulation (oTFS) on day 1 (n = 30). (B) Outcome of selected …

https://doi.org/10.7554/eLife.39151.012
Figure 5 with 1 supplement
with one supplement: The most recent plasticity event fully accounts for synaptic tenacity.

(A) Long-term survival analysis of experiments where LTD was induced 24 hr after LTP. Maximum intensity projections of mCerulean fluorescence in dendritic segment harboring a responding spine that …

https://doi.org/10.7554/eLife.39151.014
Figure 5—source data 1

Theta-frequency stimulation followed by low-freuquency stimulation.

https://doi.org/10.7554/eLife.39151.016
Figure 5—figure supplement 1
LTP followed by LTD.

(A) Outcome of all experiments where oTFS on day 0 was followed by oLFS on day 1 (n = 20). (B) Outcome of selected experiments where oTFS induced LTP (on day 0) and oLFS induced LTD of spine calcium …

https://doi.org/10.7554/eLife.39151.015

Tables

Key resources table
Reagent type
(species) or
resource
DesignationSource or referenceIdentifiersAdditional
information
Strain,
strain background
(Rattus norvegicus,
male)
WistarCharles
River
Crl:WIbred in the
animal facility,
UKE Hamburg
Strain,
strain background
(R. norvegicus, male)
WistarJanvierRjHAN:WIbred in the
animal facility,
UKE Hamburg
Genetic reagent
(Clamydomonas
reinhardtii)
ChR2(ET/TC)doi: 10.1073/pnas.1017210108channelr
hodopsin
Genetic reagent
(Aequorea victoria)
GCaMP6sdoi: 10.1038/nature12354calcium
indicator
Genetic reagent
(A. victoria)
mCeruleandoi: 10.1038/nbt945fluorescent
protein
Transfected construct
(R. norvegicus)
ChR2(ET/TC)−2A-
synaptophysin-
tdimer2
doi: 10.1073/pnas.1315926110transfection of
CA3 neurons
Recombinant
DNA reagent
rAAV2/7Vector Facility
UKE Hamburg
viral vector
Chemical
compound,
drug
APVTocris
Bioscience
CAS Number
79055-68-8
NMDA receptor
blocker
Software,
algorithm
ScanImage3.8DOI: 10.1186/1475-925X-2–13modified for
arbitrary line
scans

Additional files

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