Progressive remote memory decline coincides with parvalbumin interneuron hyperexcitability and enhanced inhibition of cortical engram cells in a mouse model of Alzheimer’s disease
- Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Netherlands
Figures
Figure 1 with 1 supplement
Progressive remote memory decline in APP/PS1 mice.
(a) Experimental design. WT and APP/PS1 mice underwent contextual fear conditioning (CFC) at 12 weeks and 16 weeks of age, and memory retrieval 30 days later at 16 weeks and 20 weeks of age, respectively. (b) At 16 weeks of age, APP/PS1 mice did not differ in freezing levels during memory retrieval compared to WT controls. Unpaired t-test: t13=0.52, p=0.61, WT (n=8), APP/PS1 (n=7). (c) At 20 weeks of age, APP/PS1 mice showed reduced freezing levels during memory retrieval compared to WT controls. Unpaired t-test: t15=3.88, *p=0.002, WT (n=8), APP/PS1 (n=9). Graphs show mean ± s.e.m.
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Figure 1—source data 1
Individual datapoints of freezing levels in Figure 1.
- https://cdn.elifesciences.org/articles/106866/elife-106866-fig1-data1-v1.xlsx
Figure 1—figure supplement 1
Amyloid beta plaque load in medial prefrontal cortex (mPFC) at 16 weeks and 20 weeks of age does not differ.
(a) Representative images at 12 weeks (left) and 16 weeks (right) in APP/PS1 mice showing DAPI staining (blue) and 6E10 amyloid plaque (magenta). Scale bars, main image: 100 µm; insets: 25 µm. (b) No difference in average amyloid plaque area (µm2) in the mPFC between APP/PS1 mice at 16 weeks and 20 weeks. Unpaired t-test: t20=0.84, p=0.41. (c) No difference in the plaque frequency in the mPFC between APP/PS1 mice at 16 weeks and 20 weeks. Mann-Whitney test: U=24, p=0.39. 16 weeks (n=6); 20 weeks (n=9). Graphs show mean ± s.e.m.
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Figure 1—figure supplement 1—source data 1
Individual datapoints of amyloid plaque in Figure 1—figure supplement 1.
- https://cdn.elifesciences.org/articles/106866/elife-106866-fig1-figsupp1-data1-v1.xlsx
Figure 2 with 1 supplement
APP/PS1 mice show an age-dependent increase in parvalbumin (PV) interneuron excitability.
(a) Schematic coronal brain section indicating the medial prefrontal cortex (mPFC) prelimbic region in dark gray, where tdTomato+ PV cells and pyramidal (PYR) cells were recorded in APP/PS1 PV-Cre tdTomato (APP/PS1) and PV-Cre tdTomato (control) mice. Representative differential interference contrast images (left) and a corresponding fluorescent image (right). fmi = forceps minor of the corpus callosum. ML = midline. Recordings were performed in 16- (b–i) and 20- (j–q) week-old mice. (b) Resting membrane potential was unaltered in PV cells at 16 weeks of age. Mann-Whitney test: U=433, p=0.98, n=29/30 cells, N=4 mice/genotype. Ctr = control. (c) Action potential (AP) firing of PV cells upon a depolarizing current step (250 pA). (d) AP frequency in PV cells in response to 0–425 pA depolarizing current steps did not differ between genotypes. Two-way repeated-measures ANOVA genotype × current F(10,390) = 0.44, p=0.93, n=29/30 cells, N=4 mice/genotype. (e) Rheobase was unchanged in PV cells. Unpaired t-test: t57=0.08, p=0.93, n=29/30 cells, N=4 mice/genotype. Ctr = control. (f) Resting membrane potential of PYR cells did not differ between genotypes. Unpaired t-test: t36=0.51, p=0.61, n=17/21 cells from N=4/6 control vs. APP/PS1 mice, respectively. Ctr = control. (g) AP firing of PYR cells upon a depolarizing current step (250 pA). (h) AP frequency in PYR cells in response to 0–250 pA depolarizing current steps did not differ between genotypes. Two-way repeated-measures ANOVA genotype × current F(10,370) = 0.25, p=0.99, n=17/21 from N=4/6 control vs. APP/PS1 mice, respectively. (i) APP/PS1 mice show a lower rheobase in PYR cells. Mann-Whitney test: U=111, *p=0.048, n=17/21 cells from N=4/6 control vs. APP/PS1 mice, respectively. Ctr = control. (j) Resting membrane potential was unaltered in PV cells at 20 weeks of age. Unpaired t-test: t35=0.93, p=0.36, n=22/15 cells from N=6/7 control and APP/PS1 mice, respectively. Ctr = control. (k) AP firing of PV cells upon a depolarizing current step (250 pA). (l) APP/PS1 mice show an increased AP frequency in PV cells in response to 0–425 pA depolarizing current steps. Two-way repeated-measures ANOVA genotype × current F(17,595) = 4.05, *p<0.0001, n=22/15 cells, N=6/7 control and APP/PS1 mice, respectively. (m) Rheobase was unchanged in PV cells. Unpaired t-test: t35=1.67, p=0.10, 22/15 cells, N=6/7 control and APP/PS1 mice, respectively. Ctr = control. (n) Resting membrane potential of PYR cells did not differ between genotypes. Unpaired t-test: t74=0.92, p=0.36, n=37/39 cells, N=9 mice/genotype. Ctr = control. (o) AP firing of PYR cells upon a depolarizing current step (250 pA). (p) AP frequency in PYR cells in response to 0–250 pA depolarizing current steps did not differ between genotypes. Two-way repeated-measures ANOVA genotype × current F(10,740) = 1.80, p=0.08, n=37/39 cells, N=9 mice/genotype. (q) APP/PS1 mice show a decrease in PYR cell rheobase. Unpaired t-test: t74=2.34, *p=0.022, n=37/39 cells, N=9 mice/genotype. Ctr = control. Graphs show mean ± s.e.m.
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Figure 2—source data 1
Individual datapoints of RMP, rheobase, and input-output curve in Figure 2.
- https://cdn.elifesciences.org/articles/106866/elife-106866-fig2-data1-v1.xlsx
Figure 2—figure supplement 1
Somatostatin (SST) cell excitability is unaltered in the medial prefrontal cortex (mPFC) of 20-week-old APP/PS1 mice.
(a) Schematic coronal brain section indicating the mPFC prelimbic region in dark gray, where AAV-hSyn::DIO-mCherry was microinjected and mCherry+ SST cells were recorded in APP/PS1 SST-Cre (APP/PS1) and SST-Cre (control) mice. Representative fluorescent image is depicted. (b) Resting membrane potential was unaltered in SST cells. Unpaired t-test: t31=0.73, p=0.47, n=17/16 cells, N=5/7 control vs. APP/PS1 mice, respectively. (c) Action potential (AP) firing of SST cells upon a depolarizing current step (250 pA). (d) AP frequency in SST cells in response to 0–250 pA depolarizing current steps did not differ between genotypes. Genotype × current two-way repeated-measures ANOVA F(10,310) = 0.23, p=0.99, n=17/16 cells, N=5/7 control vs. APP/PS1 mice. (e) Rheobase was unchanged in SST cells Mann-Whitney test: U=119, p=0.75, n=17/16 cells, N=5/7 control vs. APP/PS1 mice, respectively. Graphs show mean ± s.e.m.
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Figure 2—figure supplement 1—source data 1
Individual datapoints of RMP, rheobase, and input-output curve in Figure 2—figure supplement 1.
- https://cdn.elifesciences.org/articles/106866/elife-106866-fig2-figsupp1-data1-v1.xlsx
Figure 3 with 4 supplements
Size and reactivation of the medial prefrontal cortex (mPFC) engram ensemble, as well as parvalbumin (PV) interneuron (re)activation, are unaffected in APP/PS1 mice.
(a) Schematic representation of the viral-TRAP method. A viral cocktail of AAV-Fos-CreERT2 and Cre-dependent AAV-hSyn-DIO-mCherry was injected into the mPFC, allowing irreversible expression of mCherry upon neuronal activity and systemic injection of 4-hydroxytamoxifen (4TM). (b) Schematic timeline depicting contextual fear conditioning (CFC) and engram tagging at 12 weeks (WT n=8, APP/PS1 n=11 mice) or 16 weeks (WT n=10, APP/PS1 n=9 mice) old. On day 30 after training, mice underwent a remote memory test at 16 weeks or 20 weeks of age and were perfused 90 min later. (c) Representative images at 12–16 weeks showing PV+, mCherry+, and Fos+ cells in WT (top row) and APP/PS1 (bottom row) mice. Nissl staining (general neuronal marker) is not shown. White arrowheads indicate reactivated neurons (Fos+/mCherry+ cells). Gray arrowheads indicate PV cells that are part of the engram (PV+/mCherry+ cells). Empty arrowheads indicate reactivated PV neurons (Fos+/mCherry+/PV+ cells). Scale bar = 50 µm. Colocalization of cell-type markers is shown for 16- (d–j) and 20- (l–r) week-old mice. (d) Percentage of PV cells did not differ between genotypes. Unpaired t-test: t17=2.04, p=0.06. (e) Percentage of mCherry+ cells did not differ between genotypes. Unpaired t-test: t17=1.02, p=0.32. (f) Percentage of Fos+ cells did not differ between genotypes. Unpaired t-test: t17=0.53, p=0.60. (g) In both genotypes, Fos and mCherry overlapped above chance level. One-sample t-test: WT t7=3.59, *p=0.009; APP/PS1 t10=3.02, *p=0.013. (h) Both genotypes showed above chance overlap of PV and mCherry. One-sample t-test: WT t7=4.27, *p=0.004; APP/PS1 t10=6.69, *p<0.0001. (i) Both genotypes showed below chance colocalization of Fos and PV. One-sample t-test: WT t7=5.06, *p=0.002; APP/PS1 t10=12.99, *p<0.0001. (j) Fos, PV, and mCherry+ overlap did not differ from chance level in both genotypes. One-sample t-test: WT t7=4.05, *p=0.005; APP/PS1 t9=4.60, *p=0.001. (k) Representative images at 16–20 weeks showing PV+, mCherry+, and Fos+ cells in WT (top row) and APP/PS1 (bottom row) mice. (l) Percentage of PV cells did not differ between genotypes. Unpaired t-test: t17=0.67, p=0.51. (m) Percentage of mCherry+ cells did not differ between genotypes. Unpaired t-test: t17 = 0.42, p=0.68. (n) Percentage of Fos+ cells did not differ between genotypes. Unpaired t-test: t17=0.55, p=0.59. (o) In both genotypes, Fos and mCherry colocalized above chance level. One-sample t-test: WT t9=5.97, *p=0.0002; APP/PS1 t8=6.63, *p=0.0002. (p) Both genotypes showed above chance overlap of PV and mCherry. One-sample t-test: WT t9=6.73, *p<0.0001; APP/PS1 t8=7.05, *p=0.0001. (q) Both genotypes showed below chance colocalization of Fos and PV. One-sample t-test: WT t9=6.04, *p=0.002; APP/PS1 t8=4.07, *p=0.004. (r) Fos, PV, and mCherry overlap did not differ from chance level in both genotypes. One-sample t-test: WT t8=3.45, *p=0.009; APP/PS1 t8=4.00, *p=0.004. Graphs show mean ± s.e.m.
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Figure 3—source data 1
Individual datapoints of immunohistochemistry counts in Figure 3.
- https://cdn.elifesciences.org/articles/106866/elife-106866-fig3-data1-v1.xlsx
Figure 3—figure supplement 1
Representative example of mCherry expression in the medial prefrontal cortex (mPFC) after contextual fear conditioning (CFC) and 4-hydroxytamoxifen (4TM) treatment in APP/PS1 mice and WT controls, at 12–16 weeks and 16–20 weeks.
A mixture of AAV-Fos::CreERT2 and AAV-Syn::DIO-mCherry was injected into the mPFC. Scale bar = 200 µm. ML = midline.
Figure 3—figure supplement 2
APP/PS1 mice show remote memory impairment at 20, but not 16, weeks of age.
(a) Experimental design. WT and APP/PS1 mice underwent contextual fear conditioning (CFC) at 12 weeks and 16 weeks of age, and memory retrieval 30 days later. Mice received an injection of 4-hydroxytamoxifen (4TM) 2 hr after CFC to tag mPFC engram cells. (b) At 16 weeks of age, APP/PS1 mice did not differ in freezing levels compared to WT controls. Mann-Whitney test: U=46, p=0.38, WT (n=10), APP/PS1 (n=12). (c) At 20 weeks of age, APP/PS1 mice show reduced freezing levels compared to WT controls. Unpaired t-test: t18=2.50, *p=0.022, WT (n=10), APP/PS1 (n=10). Graphs show mean ± s.e.m.
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Figure 3—figure supplement 2—source data 1
Individual datapoints of freezing levels in Figure 3—figure supplement 2.
- https://cdn.elifesciences.org/articles/106866/elife-106866-fig3-figsupp2-data1-v1.xlsx
Figure 3—figure supplement 3
Size and reactivation of the medial prefrontal cortex (mPFC) engram ensemble, as well as parvalbumin (PV) interneuron (re)activation, are unaffected in APP/PS1 mice.
(a) Fos colocalization with mCherry+ cells (mCherry+/Nissl+) was enhanced compared to mCherry- cells (mCherry-/Nissl+) in WT and APP/PS1 mice. Two-way repeated-measures ANOVA cell population: F(1,17) = 16.3, *p=0.0009. Post hoc Bonferroni test: Control *p=0.028; APP/PS1 *p=0.016. (b) Percentage of PV+ cells in the mCherry+ population was higher than in the mCherry- population for both genotypes. Two-way repeated-measures ANOVA cell population: F(1,17) = 31.70, *p<0.0001. Post hoc Bonferroni test: WT *p=0.010; APP/PS1 *p=0.0003. (c) Percentage of Fos+ cells was higher in the mCherry-/PV- than mCherry-/PV+ population. Two-way repeated-measures ANOVA cell population: F(1,17) = 179.30, *p<0.0001; Post hoc Bonferroni test: WT *p<0.0001; APP/PS1 *p<0.0001. (d) Percentage of Fos+ cells was higher in the PV+/mCherry+ population compared to the PV+/mCherry- population in APP/PS1 and WT mice. Two-way repeated-measures ANOVA cell population: F(1,17) = 50.57, *p<0.0001; Post hoc Bonferroni test: WT *p=0.0002; APP/PS1 *p=0.0002. (e) Fos colocalization with mCherry+ cells (mCherry+/Nissl+) was enhanced compared to mCherry- cells (mCherry-/Nissl+) in WT and APP/PS1 mice. Two-way repeated-measures ANOVA cell population: F(1,17) = 56.41, *p<0.0001. Post hoc Bonferroni test: WT *p<0.0001; APP/PS1 *p=0.002. (f) Percentage of PV+ cells in the mCherry+ population was higher than in the mCherry- population for both genotypes. Two-way repeated-measures ANOVA cell population: F(1,17) = 82.15, *p<0.0001. Post hoc Bonferroni test: WT control *p<0.0001; APP/PS1 *p<0.0001. (g) Percentage of Fos+ cells was higher in the mCherry-/PV- than mCherry-/PV+ population. Two-way repeated-measures ANOVA cell population: F(1,17) = 39.15, p<0.0001; Post hoc Bonferroni test: WT *p=0.0001; APP/PS1 *p=0.004. (h) Percentage of Fos+ cells was higher in the PV+/mCherry+ population compared to the PV+/mCherry- population in APP/PS1 and WT mice. Two-way repeated-measures ANOVA cell population: F(1,17) = 17.38, *p=0.001. Post hoc Bonferroni test: WT *p=0.010; APP/PS1 *p=0.031. Graphs show mean ± s.e.m. 12-16 weeks: WT n = 8; APP/PS1 n = 11 mice. 16-20 weeks WT n = 10, APP/PS1 n = 9 mice old.
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Figure 3—figure supplement 3—source data 1
Individual datapoints of immunohistochemistry counts in Figure 3—figure supplement 3.
- https://cdn.elifesciences.org/articles/106866/elife-106866-fig3-figsupp3-data1-v1.xlsx
Figure 3—figure supplement 4
Increased reactivation of engram cells in 20- vs.16-week-old WT and APP/PS1 mice.
(a) Both genotypes showed increased overlap of Fos and mCherry at 16–20 weeks compared to 12–16 weeks. Two-way ANOVA age groups F(1,34) = 8.57, p=0.006. (b) Overlap between parvalbumin (PV) and mCherry did not differ between genotypes or age groups. Two-way ANOVA age groups F(1,34) = 2.45, p=0.13. (c) Overlap between Fos and PV did not differ between genotypes or age groups. Two-way ANOVA age groups F(1,34) = 0.05, p=0.82. (d) Fos, PV, and mCherry did not differ between genotypes or age groups. Two-way ANOVA age groups F(1,32) = 1.85, p=0.18. 12-16 weeks: WT n = 8; APP/PS1 n = 11 mice. 16-20 weeks WT n = 10, APP/PS1 n = 9 mice old.
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Figure 3—figure supplement 4—source data 1
Individual datapoints of immunohistochemistry counts in Figure 3—figure supplement 4.
- https://cdn.elifesciences.org/articles/106866/elife-106866-fig3-figsupp4-data1-v1.xlsx
Figure 4
Perisomatic parvalbumin (PV) labeling is increased on engram cells in 20-week-old APP/PS1 mice.
(a–b) Left: Representative image of WT (a) and APP/PS1 (b) mice from the 12- to 16-week groups showing PV staining and mCherry+ cells in the mPFC. Scale bar = 50 µm. Right: Examples of an mCherry- (top row) and mCherry+ (bottom row) cells. Soma outline is based on Nissl. PV signal was masked and measured inside the ring surrounding the soma. Scale bar = 10 µm. (c) PV labeling around mCherry+ cells did not differ from mCherry- cells in WT and APP/PS1 mice. Two-way repeated-measures ANOVA cell population: F(1,17) = 2.25; p=0.15; WT (n=8), APP/PS1 (n=11). (d) Left: Representative image of WT (d) and APP/PS1 (e) mice from the 16- to 20-week groups showing PV staining and mCherry+ cells in the mPFC. Scale bar = 50 µm. Right: Examples of an mCherry- (top row) and mCherry+ (bottom row) cell. Soma outline is based on Nissl. PV signal was masked and measured inside the ring surrounding the soma. Scale bar = 10 µm. (f) An increased amount of PV labeling around mCherry+ cells was found compared to mCherry- cells in APP/PS1 mice but not control mice. Two-way repeated-measures ANOVA cell population: F(1,17) = 21.74; *p=0.0002. Post hoc Bonferroni test: APP/PS1 mCherry+ vs. mCherry- *p=0.0015; WT (n=10), APP/PS1 (n=9). Graphs show mean ± s.e.m.
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Figure 4—source data 1
Individual datapoints of perisomatic parvalbumin (PV) labeling in Figure 4.
- https://cdn.elifesciences.org/articles/106866/elife-106866-fig4-data1-v1.xlsx
Figure 5
Engram cells of 20-week-old APP/PS1 mice receive increased inhibitory input.
(a) Coronal brain section indicating the medial prefrontal cortex (mPFC) region (dark gray) where AAV-Fos-CreERT2 and Cre-dependent AAV-hSyn-DIO-mCherry were injected. Mice underwent contextual fear conditioning (CFC) at 16 weeks of age, and engram cells were tagged. Thirty days after CFC, mice were re-exposed to the training context and then immediately sacrificed for whole-cell patch-clamp electrophysiology. (b) Left: Representative image showing labeled mCherry+ engram cells in the mPFC. Right: Recordings were made from mCherry+ and mCherry- pyramidal cells. fmi = forceps minor of the corpus callosum. ML = midline. (c) Example spontaneous inhibitory postsynaptic current (sIPSC) traces of mCherry+ and mCherry- for WT control and APP/PS1 mice. (d) Example spontaneous excitatory postsynaptic current (sEPSC) traces of mCherry+ and mCherry- cells for WT and APP/PS1 mice. (e) Frequency of sIPSCs differed between mCherry+ and mCherry- cells in APP/PS1, but not WT, mice. Two-way repeated-measures ANOVA genotype × cell type F(1,43) = 5.44, *p=0.024. Post hoc Bonferroni APP/PS1 mCherry+ vs. mCherry- *p=0.011. n=22 per cell type from N=6 WT mice, n=23 per cell type from N=7 APP/PS1 mice. (f) sIPSC amplitude did not differ between cell type and genotype. Two-way repeated measure ANOVA cell-type F(1,43) = 1.24, p = 0.27. Two-way repeated measure ANOVA genotype F(1,43) = 0.01, p = 0.93. n = 22 per cell-type from N = 6 WT mice, n = 23 per cell-type from N = 7 APP/PS1 mice(g) Frequency of sEPSCs was enhanced in mCherry+ cells compared to mCherry- cells in both genotypes. Two-way repeated-measures ANOVA cell type F(1,36) = 7.26, *p=0.011, n=20 per cell type from N=6 WT mice, n=23 per cell type from N=7 APP/PS1 mice. (h) sEPSC amplitude did not differ between cell type and genotype. Two-way repeated measure ANOVA cell-type F(1,40) = 0.32, p = 0.57. Two-way repeated measure ANOVA genotype F(1,40) = 0.03, p = 0.86. n = 20 per cell type from N = 6 WT mice, n = 23 per cell-type from N = 7 APP/PS1 mice. Graphs show mean ± s.e.m.
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Figure 5—source data 1
Individual datapoints of spontaneous inhibitory postsynaptic current (sIPSC) and spontaneous excitatory postsynaptic current (sEPSC) measurements in Figure 5.
- https://cdn.elifesciences.org/articles/106866/elife-106866-fig5-data1-v1.xlsx
Tables
Key resources table
| Reagent type (species) or resource | Designation | Source or reference | Identifiers | Additional information |
|---|---|---|---|---|
| Strain, strain background construct (M. musculus) | APP/PS1, APPswe,PSEN1de9 | The Jackson Laboratory | Stock number 004462, RRID:MMRRC_034829-JAX | Male |
| Strain, strain background (M. musculus) | PV-Cre, B6.129P2-Pvalbtm1(cre)Arbr/J | The Jackson Laboratory | Stock number 017320 RRID:IMSR_JAX:017320 | Male |
| Strain, strain background (M. musculus) | SST-Cre, Ssttm2.1(cre)Zjh/J | The Jackson Laboratory | Stock number 013044 RRID:IMSR_JAX:013044 | Male |
| Strain, strain background (M. musculus) | R26AI14+, B6.Cg-Gt(ROSA)26Sortm14(CAG-tdTomato)Hze/J | The Jackson Laboratory | Stock number 007914 RRID:IMSR_JAX:007914 | Male |
| Genetic reagent | AAV-Fos::CreERT2 | Matos et al., 2019 | Serotype 5 | |
| Genetic reagent | AAV-hSyn::DIO-mCherry | Matos et al., 2019 | Serotype 5 | |
| Antibody | Anti-Fos (rabbit) | Synaptic Systems | #226008 | 1:1000 |
| Antibody | Anti-Parvalbumin (mouse) | Chemicon/ Millipore | MAB1572, RRID:AB_2174013 | 1:2000 |
| Antibody | Anti-6E10 (mouse) | BioLegend | SIG-39320, RRID:AB_662798 | 1:1000 |
| Antibody | Anti-rabbit Alexa Fluor 488 (goat) | ThermoFisher Scientific | A-11008, RRID:AB_143165 | 1:400 |
| Antibody | Anti-mouse Alexa Fluor 405 (goat) | Invitrogen | A-31553, RRID:AB_221604 | 1:400 |
| Antibody | NeuroTrace 530/6115 Red fluorescent Nissl | ThermoFisher Scientific | N21483, RRID:AB_2572212 | 1:200 |
| Antibody | Anti-mouse 647 (goat) | Invitrogen | A-21245, RRID:AB_2535813 | 1:400 |
| Chemical compound, drug | Temgesic | RB Pharmaceuticals | 0.1 mg/kg | |
| Chemical compound, drug | Lidocaine | Sigma-Aldrich Chemie N.V. | 2% | |
| Chemical compound, drug | 4 -hydroxytamoxifen | HelloBio | HB6040 | 25 mg/kg, i.p. |
| Chemical compound, drug | DMSO | Sigma Aldrich Chemie N.V. | D8418 | |
| Chemical compound, drug | 2%Tween80 | Sigma Aldrich Chemie N.V. | P1754 | |
| Software, Algorithm | Ethovision XT | Noldus | Video analysis | |
| Software, algorithm | Fiji | ImageJ | Version 2.14.0/1.54 p | Image analysis |
| Software, algorithm | Graphpad Prism | GraphPad Software Inc | Version 10.4.1 | Analysis and data visualization |
| Software, algorithm | MATLAB | Mathworks | Electrophysiology and image analysis | |
| Software, algorithm | Python | Python Software Foundation | Image analysis | |
| Software, algorithm | IGOR Pro | WaveMetrics | Version 8.0 | Electrophysiology analysis |
Additional files
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Supplementary file 1
Supplementary tables describing parvalbumin (PV) and pyramidal (PYR) cell properties at 16 weeks and 20 weeks, as well as somatostatin (SST) cell properties at 20 weeks.
- https://cdn.elifesciences.org/articles/106866/elife-106866-supp1-v1.docx
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MDAR checklist
- https://cdn.elifesciences.org/articles/106866/elife-106866-mdarchecklist1-v1.docx
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Source data 1
Individual datapoints of parvalbumin (PV) cell properties at 16 weeks in Supplementary file 1, table 1A.
- https://cdn.elifesciences.org/articles/106866/elife-106866-data1-v1.xlsx
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Source data 2
Individual datapoints of pyramidal (PYR) cell properties at 16 weeks in Supplementary file 1, table 1B.
- https://cdn.elifesciences.org/articles/106866/elife-106866-data2-v1.xlsx
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Source data 3
Individual datapoints of parvalbumin (PV) cell properties at 20 weeks in Supplementary file 1, table 1C.
- https://cdn.elifesciences.org/articles/106866/elife-106866-data3-v1.xlsx
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Source data 4
Individual datapoints of pyramidal (PYR) cell properties at 20 weeks in Supplementary file 1, table 1D.
- https://cdn.elifesciences.org/articles/106866/elife-106866-data4-v1.xlsx
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Source data 5
Individual datapoints of somatostatin (SST) cell properties at 20 weeks in Supplementary file 1, table 1E.
- https://cdn.elifesciences.org/articles/106866/elife-106866-data5-v1.xlsx
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Progressive remote memory decline coincides with parvalbumin interneuron hyperexcitability and enhanced inhibition of cortical engram cells in a mouse model of Alzheimer’s disease
eLife 14:RP106866.
https://doi.org/10.7554/eLife.106866.3
