Impairment of Spike-Timing-Dependent Plasticity at Schaffer Collateral-CA1 Synapses in Adult APP/PS1 Mice Depends on Proximity of Aβ Plaques
Abstract
:1. Introduction
2. Results
2.1. Low Repeat STDP Paradigms Induced Timing-Dependent (t-) LTP in Adult WT Mice
Low Repeat STDP Paradigm Induced Timing-Dependent (t-) LTP in Adult APP/PS1 Mice
2.2. High Repeat STDP Stimulation Paradigm Induced t-LTP in Adult APP/PS1 Mice
2.3. T-LTP Induced with 6× 1:4 Stimulation at SC-CA1 Synapses in Adult APP/PS1 Mice is Impaired Selectively in CA1 Neurons Located Near to Aβ Plaques
2.4. Chronic Fingolimod Treatment of APP/PS1 Mice Does Not Rescue Impaired t-LTP in CA1 Neurons Located in the Vicinity of Aβ Plaques
2.5. CA1 Pyramidal Neurons in APP/PS1 Animals Showed Comparable Basal Electrical Properties as WT Littermates, Irrespective of Aβ Plaques Location
2.6. APP/PS1 Mice Show Differences in Spontaneous Excitatory Postsynaptic Currents (EPSCs)
3. Discussion
3.1. Timing-Dependent LTP in 6-Month-Old Adult WT Mice
3.2. Intact Timing-Dependent LTP in Adult APP/PS1 Mice When Aβ Plaque Location Was Not Resolved
3.3. Impaired t-LTP in CA1 Neurons Located in the Vicinity of Aβ Plaques in Adult APP/PS1 Mice
3.4. Chronic Fingolimod Treatment Did Not Rescue Impaired t-LTP in APP/PS1 Mice
3.5. Unaltered Basal Properties of CA1 Neurons in APP/PS1 Mice
4. Conclusions
5. Materials and Methods
5.1. Animals
5.2. Hippocampal Slice Preparation and Maintenance
5.3. Aβ Plaque Staining with Methoxy-X04 in Acute Hippocampal Slices
5.4. Chronic Fingolimod Treatment of APP/PS1 Mice
5.5. Electrophysiology in Acute Hippocampal Slices
5.6. Data Acquisition and Data Analyses
5.7. Whole Cell EPSC Recordings
5.8. Statistics
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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STDP Paradigm (Presyn. Stim.: Postsyn. AP) | No. of Repeats, Frequency | Normalized t-LTP Magnitude (EPSP Slope %) | ||
---|---|---|---|---|
C57Bl/6J Mice | WT Littermates | APP/PS1 Mice | ||
0:0 (negative control) | 106.9 ± 7.7% (n = 11/N = 10) | |||
1 EPSP:4 AP | 6×, 0.5 Hz | 157.9 ± 14.2% (n = 11/N = 8) *,# | 153.8 ± 13.5% (n = 13/N = 7) * | 138.9 ± 8.7% (n = 12/N = 6) * |
1 EPSP:1 AP | 6×, 0.5 Hz | 134.3 ± 7.5% (n = 13/N = 10) * | ||
1 EPSP:4 AP | 35×, 2 Hz | 139.1 ± 9.5% (n = 10/N = 10) *# | ||
1 EPSP:1 AP | 100×, 2 Hz | 142.0 ± 7.9% (n = 13/N = 12) *# | 130.9 ± 8.5% (n = 11/N = 5) * | 157.3 ± 14.9% (n = 9/N = 5) * |
Aβ Plaque Staining (Methoxy-X04) | ||||
WT littermates | APP/PS1, cells near to Aβ (<200 µm) | APP/PS1, cells distant from Aβ (>200 µm) | ||
1 EPSP:4 AP | 6×, 0.5 Hz | 135.8 ± 10.6% (n = 16/N = 9) * | 92.4 ± 9.1% (n = 12/N = 9) # | 129.6 ± 9.6% (n = 8/N = 4) * |
Chronic Fingolimod Treatment of APP/PS1 Mice | ||||
WT littermates + fingolimod | AD near + Fingolimod | |||
1 EPSP:4 AP | 6×, 0.5 Hz | 169.9 ± 20.1% (n = 12/N = 7) * | 111.1 ± 10.2% (n = 16/N = 7) |
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Garad, M.; Edelmann, E.; Leßmann, V. Impairment of Spike-Timing-Dependent Plasticity at Schaffer Collateral-CA1 Synapses in Adult APP/PS1 Mice Depends on Proximity of Aβ Plaques. Int. J. Mol. Sci. 2021, 22, 1378. https://doi.org/10.3390/ijms22031378
Garad M, Edelmann E, Leßmann V. Impairment of Spike-Timing-Dependent Plasticity at Schaffer Collateral-CA1 Synapses in Adult APP/PS1 Mice Depends on Proximity of Aβ Plaques. International Journal of Molecular Sciences. 2021; 22(3):1378. https://doi.org/10.3390/ijms22031378
Chicago/Turabian StyleGarad, Machhindra, Elke Edelmann, and Volkmar Leßmann. 2021. "Impairment of Spike-Timing-Dependent Plasticity at Schaffer Collateral-CA1 Synapses in Adult APP/PS1 Mice Depends on Proximity of Aβ Plaques" International Journal of Molecular Sciences 22, no. 3: 1378. https://doi.org/10.3390/ijms22031378