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Altered hippocampal-prefrontal communication during anxiety-related avoidance in mice deficient for the autism-associated gene Pogz

  1. Margaret M Cunniff
  2. Eirene Markenscoff-Papadimitriou
  3. Julia Ostrowski
  4. John LR Rubenstein
  5. Vikaas Singh Sohal  Is a corresponding author
  1. Department of Psychiatry, Weill Institute for Neurosciences, and Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, United States
Research Article
Cite this article as: eLife 2020;9:e54835 doi: 10.7554/eLife.54835
7 figures, 4 tables and 1 additional file

Figures

Figure 1 with 3 supplements
Pogz+/- mice exhibit reduced avoidance in the elevated plus maze (EPM).

(A, B) Occupancy plot for a 15 min EPM session for a representative wildtype (A) and Pogz+/- (B) mouse. (C) Ratio of time spent in open vs. closed arms of the EPM. Wilcoxon rank-sum test, U = −2.8857, p=0.003, WT N = 18, Het N = 27. (D) Total distance traveled during EPM sessions. Wilcoxon rank-sum test U = −1.9434, p=0.35, WT N = 16, Het N = 23. (E) Total time spent in exposed areas of EPM, open arms: statistic = −3.0753, p=0.001, center: U = −2.2112, p=0.02. Wilcoxon rank-sum test, WT N = 18, Het N = 27. (F) Total number of head dips for each mouse, U = −1.9434, p=0.03. Wilcoxon rank-sum test, WT N = 14, Het N = 14. (G) Number of open arm entries, U = −0.9993, p=0.32. Wilcoxon rank-sum test, WT N = 16, Het N = 23. (H) Average duration of each open arm visit, U = −1.984, p=0.047. Wilcoxon rank-sum test, WT N = 16, Het N = 23.

Figure 1—figure supplement 1
Sex differences do not account for elevated-plus maze (EPM) phenotypes.

EPM metrics divided by sex. For normally distributed data, two-way ANOVA was used to separate effects of genotype and sex. For non-normal data, effects of sex were tested by correcting all values by the median wildtype value for that sex. (A) Ratio of time in open vs closed arms. Pearson’s normality test, statistic = 8.4985, p=0.014. Genotype rank-sum test for sex-adjusted values, U = −2.4455, p=0.014. Rank-sum test for sex difference in Het mice, U = 0.52698, p=0.60. WT N = 12 males, 4 females. Het N = 10 males, 17 females. (B) Total distance traveled in EPM. Pearson’s normality test, statistic = 14.70185, p=0.00064. Genotype rank-sum test for sex-adjusted values, U = −0.2594, p=0.79. WT N = 12 males, four females. Het N = 9 males, 14 females. (C) Head dips. Pearson’s normality test, statistic = 2.0271, p=0.44. Two-way ANOVA, effect of genotype, F = 4.776, p=0.02, effect of sex, F = 0.88, p=0.81, interaction, F = 0.365, p=0.36. Rank-sum test for sex difference in Het mice, U = −0.6123, p=0.54. WT N = 10 males, 4 females. Het N = 8 males, 6 females. (D) Number of open arm entries. Pearson’s normality test, statistic = 3.02627, p=0.22. Two-way ANOVA, effect of genotype, F = 0.264, p=0.61, effect of sex, F = 0.85, p=0.32, interaction, F = 1.31, p=0.26. WT N = 12 males, 4 females. Het N = 9 males, 14 females. (E) Average open arm visit length. Pearson’s normality test, statistic = 3.16358, p=0.22. Two-way ANOVA, effect of genotype, F = 3.42, p=0.07, effect of sex, F = 0.479, p=0.49, interaction, F = 0.092, p=0.76. WT N = 12 males, 4 females. Het N = 9 males, 14 females. (F) Total time in open arms. Pearson’s normality test, statistic = 6.4703, p=0.040. Genotype rank-sum test for sex-adjusted values, U = −2.479, p=0.013. Rank-sum test for sex difference in Het mice, U = 0.6527, p=0.61. WT N = 12 males, 4 females. Het N = 10 males, 17 females. (G) Total time in center. Pearson’s normality test, statistic = 1.2337, p=0.54. Two-way ANOVA, effect of genotype, F = 3.06, p=0.087, effect of sex, F = 1.14, p=0.29, interaction, F = 0.50, p=0.48. WT N = 12 males, 4 females. Het N = 10 males, 17 females.

Figure 1—figure supplement 2
Other behavioral assays in Pogz+/- mice.

(A) Time that Pogz+/- mice or wild-type littermates spend interacting with a novel juvenile conspecific, U = 0.96, p=0.34. Wilcoxon rank sum, WT N = 7, Het N = 7. (B) Time that Pogz+/- mice or wild-type littermates spend interacting with a novel object, U = −0.063, p=0.95. Wilcoxon rank sum, WT N = 7, Het N = 7. (C) Number of marbles buried by Pogz+/- mice or wild-type littermates during 20 min, U = 0.7522, p=0.45. Wilcoxon rank sum, WT N = 8, Het N = 7. (D) Distance traveled in an open field by Pogz+/- mice or wild-type littermates, U = −1.4289, p=0.15. Wilcoxon rank sum, WT N = 14, Het N = 17. (E) Schematic of the T-maze delayed match to sample task. Mice must recall the direction of the forced run during the sample phase to successfully obtain reward from the opposite arm during the choice phase. (F) Number of trials Pogz+/- mice or wild-type littermates need to reach a learning criterion (80% accuracy) in the T-maze task, U = −0.5222, p=0.60. Wilcoxon rank sum, WT N = 5, Het N = 5. (G) Schematic of the odor-texture rule shift task. Mice must initially learn that a texture cue signals the location of a hidden food reward. Once they learn this initial rule, there is an extra-dimensional rule shift such that an odor now signals the reward location. (H) Number of trials Pogz+/- mice or wild-type littermates need to reach a learning criterion (80% accuracy) during the initial association or rule shift, IA: U = −0.1443, p=0.89; RS: U = 0.1443, p=0.89. Wilcoxon rank sum, WT N = 4, Het N = 4.

Figure 1—figure supplement 3
Distributions of sex and age for WT and Pogz Het mice used in all experiments.

Age and sex breakdown for all experimental animals; age listed at date of testing. (A) Elevated-plus maze (EPM) sex. WT males: 13, Het males: 10, WT females: 6, Het females: 17. (B) EPM age. WT: 72 ± 13 days, Het: 72 ± 22 days. (C) Rule shift sex. WT males: 3, Het males: 2, WT females: 2, Het females: 2. (D) Rule shift age. WT: 68 ± 3 days, Het: 68 ± 3 days. (E) Marble burying sex. WT males: 6, Het males: 5, WT females: 2, Het females: 2. (F) Marble burying age. WT: 108 ± 69 days, Het: 115 ± 72 days. (G) Social interaction and novel object exploration sex. WT males: 4, Het males: 4, WT females: 3, Het females: 3. (H) Social interaction and novel objection exploration age. WT: 69 ± 8 days, Het: 65 ± 7 days. (I) Open field sex. WT males: 10, Het males: 8, WT females: 4, Het females: 9. (J) Open field age. WT: 69 ± 14 days, Het: 67 ± 11 days. (K) T-maze sex. WT males: 3, Het males: 3, WT females: 2, Het females: 2. (L) T-maze age. WT: 61 ± 40 days, Het: 61 ± 40 days. (M) Patch clamp recordings sex. WT males: 10, Het males: 8, WT females: 10, Het females: 6. (N) Patch clamp recordings age. WT: 110 ± 18 days, Het: 11 ± 22 days. (O–P) Local field potential recordings sex. WT males: 4, Het males: 3, WT females: 2, Het females: 4. (P) Local field potential recordings age. WT: 99 ± 36 days, Het: 121 ± 34 days.

Figure 2 with 2 supplements
Pogz+/- mice have reduced vHPC-PFC theta synchrony both at baseline and in the elevated-plus maze (EPM).

(A) Recording schematic and examples of raw local field potential traces. (B) Z-scored theta band weighted-phase locking index (WPLI) as mice approach the center of the EPM. Linear mixed effects model using timepoint (−3,–1.5, 0, and +1.5 s relative to center zone entry), genotype, mouse, and timepoint X genotype interaction as fixed factors and individual run as a random factor, p=0.00039 for timepoint X genotype interaction, t-statistic = −3.55, DF = 2355 for fixed factors, n = 274 and 316 closed-center runs from 7 WT mice and 6 Het mice, respectively. Wilcoxon rank-sum test for t = 0: U = 3.3738, p=0.0007, for t = 1.5: U = 2.0275, p=0.043 (n = 274 closed-center runs from 7 WT mice and 316 from 6 Het mice). (C) Average theta band WPLI in the open vs. closed arms of the EPM. Two-way ANOVA including arm and genotype as factors - significant effect of genotype: p=0.03 (d.f. = 1, N = 6 WT and 7 Het mice, F = 5.66). (D) Theta band WPLI for mice in their homecages: U = 2.2417, p=0.031 (Wilcoxon rank-sum with N = 6 WT and 7 Het mice).

Figure 2—figure supplement 1
LFP power in various frequency bands in the vHPC and mPFC is not changed in Pogz+/- mice.

(A) mPFC LFP power in home cage: θ (4–12 Hz), U = −0.3202, p=0.81; β (12–30 Hz), U = 0, p=0.94; low γ (30–55 Hz), U = −0.801, p=0.47; high γ (65–100 Hz), U = −0.3202, p=0.8. (B) vHPC LFP power in the home cage: θ, U = −1.281, p=0.23; β, U = −1.761, p=0.093; low γ, U = −1.441, p=0.17; high γ, U = 0, p=0.94. (C) mPFC LFP power in EPM closed arm: θ, U = −0.142, p=0.88; β, U = 0, p=1.0; low γ, U = 1.285, p=0.20; high γ, U = 1.642, p=0.10. (D) vHPC LFP power in EPM closed arm: θ, U = −1.142, p=0.25; β, U = −1.428, p=0.15; low γ, U = −0.714, p=0.47; high γ, U = 0.1428, p=0.89. (E) mPFC LFP power in EPM open arm: θ, U = −0.142, p=0.89; β, U = −0.1428, p=0.89; low γ, U = 0, p=1.0; high γ, U = 1.428, p=0.15. (F) vHPC LFP power in EPM open arm: θ, U = −1.0, p=0.32; β, U = −1.285, p=0.20; low γ, U = −1.142, p=0.25; high γ, U = 0.0, p=1.0. All statistics from Wilcoxon Rank-Sum Tests, WT N = 6, Het N = 7.

Figure 2—figure supplement 2
Location of LFP electrodes (A–C) mPFC electrode locations.

(A) AP 1.745, (B) AP 1.645, (C) AP 1.42. (D–F) vHPC electrode locations. (D) AP −2.78, (E) AP −2.98, (F) AP −3.18. Images from Allen Mouse Brain Atlas (Lein et al., 2007).

Figure 3 with 1 supplement
An unbiased, data-driven approach confirms that theta-frequency vHPC-mPFC communication is behaviorally-relevant and deficient in Pogz+/- mice.

(A) Example weight vectors showing how various LFP features (x-axis) contribute to different independent components (ICs) in one mouse. The y-axis shows the weight of each feature. (B) Correlation matrix showing the similarity of weight vectors corresponding to different ICs, from all mice. (C) Binarized version of the correlation matrix showing pairs of ICs that have a correlation coefficient > 0.7. (D) Example weights vectors (light, colored traces) for ICs from one cluster. This cluster is characterized by strong weights for cross-frequency coupling between vHPC theta activity and higher-frequency activity in either vHPC or mPFC. The bold black trace shows the average of these weight vector. (F) The projection of network activity onto the characteristic (averaged) weight vector (from E) as a function of time during approaches to the center of the EPM, for wild-type or Pogz+/- mice. As mice approach the center, activity in this characteristic IC rises sharply and reaches a peak in WT mice, but this is absent in Pogz+/- mice. Linear mixed effects model using timepoints (t = 0 vs. baseline based on the average of the first/last points), mouse, genotype, and timepoint X genotype interaction as fixed factors, and individual runs as random factors, timepoint X genotype interaction p=0.01, DF = 147, t-statistic = 2.60; Wilcoxon rank-sum test for t = 0: p=0.007, U = 2.6864; n = 39 closed-center-open runs from 6 WT mice and 37 runs from 7 Het mice.

Figure 3—figure supplement 1
Activity in conserved independent components (ICs) during approaches to the center of the EPM.

(A–C) Weights for the three ICs that were conserved across mice, i.e., were defined by clusters of ICs that were from different mice but were very similar, as indicated by strong correlations (we averaged the weights of the individual ICs in each cluster to obtain the weights shown here). (A) Shows weights for the characteristic IC highlighted in Figure 3, which corresponds to cross-frequency phase-amplitude coupling between hippocampal-theta and beta or gamma activity in the hippocampus or PFC. The characteristic IC shown in (B) corresponds to cross-frequency phase-amplitude coupling between prefrontal theta and beta or gamma activity in the hippocampus or PFC. The characteristic IC shown in (C) corresponds to broadband power across all frequency bands in the hippocampus and PFC. (D–F) The projection of network activity onto each characteristic (averaged) weight vector (from A-C) as a function of time during approaches to the center of the EPM, for wild-type or Pogz+/- mice. The first and third characteristic ICs (panels D and F) both exhibit increased activity during center approaches in WT mice, but this increase was absent/deficient in Pogz mutant mice: U = 2.6864, p=0.007 and U = 2.4266, p=0.015 for IC #1 and IC #3, respectively, by Wilcoxon rank-sum test, n = 39 closed-center-open runs from 6 WT mice and 37 runs from 7 Het mice. Linear mixed effects model for IC #1 is described in Figure 3E. For IC #3, the same linear mixed effects model yields p=0.052 (t statistic = 1.96) for the timepoint X genotype interaction.

Figure 4 with 1 supplement
Excitatory hippocampal input to prefrontal fast-spiking interneurons (FSINs) is reduced in Pogz mutants.

(A, B) Representative examples of optically-evoked excitatory post-synaptic currents (oEPSCs) recorded from prefrontal FSINs in wildtype (A) or Pogz+/- mice (B). (C, D) Representative traces of optically-evoked excitatory post-synaptic potentials (oEPSPs) and action potentials recorded from FSINs in wildtype (C) or Pogz+/- mice (D). (E) The total oEPSC charge in FSINs is reduced in Pogz+/- mice, U = 2.7652, p=0.006. (F) The paired- pulse ratio (PPR) for oEPSCs is reduced in Pogz+/- FSINs, U = 2.128, p=0.03. (G) The latency of the first optically-evoked action potential is increased in Pogz+/- FSINs, U = −2.490, p=0.013. (H) The number of action potentials elicited by oEPSPs is non-significantly altered, U = 1.766, p=0.08. In E-H, different hues correspond to specific mice, and squares indicate datapoints from cells that were used for the representative traces shown in A-D. All p-values from Wilcoxon rank sum, WT N = 6 animals, n = 11 cells. Het N = 3 animals, n = 7 cells.

Figure 4—figure supplement 1
Intrinsic properties of prefrontal FSIN are not changed in Pogz+/- mice.

(A, B) Representative examples of FSIN responses to current injection in WT (left) or Pogz+/- (right) mice. (C) Membrane resting potential, U = −0.6792, p=0.50. (D) Input resistance, U = −0.7698, p=0.44. (E) Action potential halfwidth, U = −0.724, p=0.47. (F) Maximum firing rate, U = 0.6792, p=0.50. All p-values from Wilcoxon rank sum, WT N = 6 animals, n = 11 cells. Het N = 3 animals, n = 7 cells.

Figure 5 with 1 supplement
Excitatory hippocampal input to prefrontal pyramidal neurons is not changed in Pogz mutants.

(A, B) Representative examples of optically-evoked excitatory post-synaptic currents (oEPSCs) recorded from prefrontal pyramidal neurons in wildtype (A) or Pogz+/- mice (B). (C, D) Optically-evoked excitatory post-synaptic potentials (oEPSPs) and action potentials in wildtype (C) or Pogz+/- (D) pyramidal neurons. (E) Total oEPSC charge in pyramidal neurons, U = 1.0736, p=0.28. (F) Paired-pulse ratio for oEPSCs in pyramidal neurons, U = 1.4347, p=0.15 (G) Latency to first optically-evoked action potential in pyramidal neurons, U = −0.305, p=0.76. (H) Number of action potentials elicited by oEPSPs in pyramidal neurons, U = 0.2822, p=0.78. In E-H, different hues correspond to specific mice, and squares indicate datapoints from cells that were used for the representative traces shown in A-D. All p-values from Wilcoxon rank sum, WT N = 13 animals, n = 17 cells. Het N = 8 animals, n = 11 cells.

Figure 5—figure supplement 1
Pyramidal cell properties are not changed in Pogz+/-mice.

(A, B) Representative examples of pyramidal neuron responses to current injection in WT (left) or Pogz+/- (right) mice. (C) Membrane resting potential, U = 0.0705, p=0.94. (D) Input resistance, U = −0.258, p=0.80. (E) Action potential halfwidth, U = 0.7291, p=0.46. (F) Maximum firing rate, U = 0.0940, p=0.93. All p-values from Wilcoxon rank sum, WT N = 13 animals, n = 17 cells. Het N = 8 animals, n = 11 cells.

Figure 6 with 2 supplements
Reducing the excitatory drive onto prefrontal FSINs impairs the transmission of hippocampal inputs.

(A) Computational model schematic. Both a model pyramidal neuron (triangle) and a model FSIN (circle) receive simulated hippocampal input (which is rhythmically modulated at 8 Hz), and additional input which represents noise. (B) The correlation between the pyramidal neuron output spike rate and the rate of either noise inputs (dark blue) or hippocampal spikes (turquoise), as functions of a single parameter which represents how strongly hippocampal and noise inputs excite the model FSIN. (C) The spike rate of the model pyramidal neuron (turquoise) and FSIN (dark blue) as functions of a single parameter representing how strongly hippocampal and noise inputs excite the model FSIN. (D) The ratio of the correlation between pyramidal neuron output spikes and either hippocampal input or noise input.

Figure 6—figure supplement 1
Adding feedforward disinhibition does not change the relationship between inhibitory strength and hippocampal correlation.

(A) Schematic of the computational model including cells and input sources. In comparison to the original model (Figure 6), this model includes an additional interneuron (ellipse) which receives feedforward excitation representing noise or hippocampal input. This new interneuron inhibits the first interneuron (circle), providing disinhibition. (B) The correlation between the pyramidal neuron output spike rate and the rate of either noise inputs (dark blue) or hippocampal spikes (turquoise), as functions of a single parameter which represents how strongly hippocampal and noise inputs excite the model FSIN. (C) The spike rate of the model pyramidal neuron (turquoise) and FSIN (dark blue) as functions of a single parameter representing how strongly hippocampal and noise inputs excite the model FSIN. (D) The ratio of the correlation between pyramidal neuron output spikes and either hippocampal input or noise input.

Figure 6—figure supplement 2
The effect of reducing inhibition on the transmission of signals across hippocampal-prefrontal synapses depends on the frequency of hippocampal input.

We simulated the same model shown in Figure 6 using non-rhythmic noise together with hippocampal input that varied sinusoidally at various-frequencies: 0.5 Hz (A, B), 2 Hz (C, D), 8 Hz (E, F), or 40 Hz (G, H). Similar to Figure 6 and Figure 6—figure supplement 1, we plotted the correlation between the pyramidal neuron output spike rate and the rate of either noise inputs (dark blue) or hippocampal spikes (turquoise), as functions of how strongly hippocampal and noise inputs excite the model FSIN. Inhibition serves to enhance the signal-to-noise ratio when hippocampal input is modulated at 2 or 8 Hz, but not for higher (40 Hz) or lower (0.5 Hz) frequencies.

Author response image 1

Tables

Table 1
Single frequency LFP measures used as features in PCA/ICA analysis.
MeasureRegionFrequencies
PowerHPCTheta (4–12 Hz)
Beta (13–30 Hz)
Low Gamma (30–55 Hz)
High Gamma (65–100 Hz)
PFCTheta (4–12 Hz)
Beta (13–30 Hz)
Low Gamma (30–55 Hz)
High Gamma (65–100 Hz)
Amplitude CovariationHPC-PFCTheta (4–12 Hz)
Beta (13–30 Hz)
Low Gamma (30–55 Hz)
High Gamma (65–100 Hz)
Weighted-Phase LockingHPC-PFCTheta (4–12 Hz)
Beta (13–30 Hz)
Low Gamma (30–55 Hz)
  1. High Gamma (65–100 Hz).

Table 2
Multiple frequency LFP measures used as features in PCA/ICA analysis.
MeasureRegionsFrequencies
Cross-Frequency CouplingHPC (low) → PFC (high)Theta (2–6 Hz) → Beta (13–30 Hz)
Theta (2–6 Hz) → Low Gamma (30–55 Hz)
Theta (2–6 Hz) → High Gamma (65–100 Hz)
Alpha (6–10 Hz) → Beta (13–30 Hz)
Alpha (6–10 Hz) → Low Gamma (30–55 Hz)
Alpha (6–10 Hz) → High Gamma (65–100 Hz)
PFC (low) → HPC (high)Theta (2–6 Hz) → Beta (13–30 Hz)
Theta (2–6 Hz) → Low Gamma (30–55 Hz)
Theta (2–6 Hz) → High Gamma (65–100 Hz)
Alpha (6–10 Hz) → Beta (13–30 Hz)
Alpha (6–10 Hz) → Low Gamma (30–55 Hz)
Alpha (6–10 Hz) → High Gamma (65–100 Hz)
HPC (low) → HPC (high)Theta (2–6 Hz) → Beta (13–30 Hz)
Theta (2–6 Hz) → Low Gamma (30–55 Hz)
Theta (2–6 Hz) → High Gamma (65–100 Hz)
Alpha (6–10 Hz) → Beta (13–30 Hz)
Alpha (6–10 Hz) → Low Gamma (30–55 Hz)
Alpha (6–10 Hz) → High Gamma (65–100 Hz)
PFC (low) → PFC (high)Theta (2–6 Hz) → Beta (13–30 Hz)
Theta (2–6 Hz) → Low Gamma (30–55 Hz)
Theta (2–6 Hz) → High Gamma (65–100 Hz)
Alpha (6–10 Hz) → Beta (13–30 Hz)
Alpha (6–10 Hz) → Low Gamma (30–55 Hz)
  1. Alpha (6–10 Hz) → High Gamma (65–100 Hz).

Key resources table
Reagent type
(species) or
resource
DesignationSource or
reference
IdentifiersAdditional
information
Strain, strain background (Mus. Musculus)C57BL6/JJackson LabsStock No: 000664
Genetic reagent (Mus. Musculus)PogZ+/-Rubenstein Lab
Recombinant DNA reagentAAV5-CaMKIIa-hChR2(H134R)-EYFPUNC Vector CoreRRID:Addgene_26969
Recombinant DNA reagentAAV5-DlxI12b-mCherryVirovek, Sohal lab
Software, algorithmSirenia AcquisitionPinnacleRRID:SCR_016183
Software, algorithmANY-maze tracking softwareANY-mazeRRID:SCR_014289
Software, algorithmPythonPythonRRID:SCR_008394Packages: Numpy, Scipy,
Matplotlib, Seaborn
Software, algorithmMATLABMathworksRRID:SCR_001622Signal Processing Toolbox
Software, algorithmPClampMolecular DevicesRRID:SCR_011323
Table 3
Details of all statistical tests N indicates biological replicates for example individual cells or behavior trials.
FigureDataTestP valWT AnimalsHet AnimalsWT nHet n
Figure 1CZone occupancyWilcoxon rank sum0.0031827
Figure 1DEPM DistanceWilcoxon rank sum0.351623
Figure 1EOpen timeWilcoxon rank sum0.0011827
Figure 1ECenter timeWilcoxon rank sum0.021827
Figure 1FHead dipsWilcoxon rank sum0.031414
Figure 1GOpen entriesWilcoxon rank sum0.321623
Figure 1HOpen visitWilcoxon rank sum0.0471623
Figure 2BWPLI, t = 0Wilcoxon rank sum0.000767274316
Figure 2BWPLI, t = 1.5Wilcoxon rank sum0.04367274316
Figure 2BWPLI, t = −3,–1.5, 0, +1.5
during closed-center runs
Linear mixed effects model timepoint mouse genotype timept X genotype0.0026
0.47
0.059
0.0004
67274316
Figure 2CAvg zone WPLI, genotypeTwo-way ANOVA0.0367
Figure 2CAvg zone WPLI, zoneTwo-way ANOVA0.06367
Figure 2CAvg zone WPLI, interactionTwo-way ANOVA0.9867
Figure 2DTheta WPLIWilcoxon rank sum0.03167
Figure 3EIC zone projection, t = 0Wilcoxon rank sum0.007673937
Figure 3EICA zone projection t = 0 vs. baseline (average of first and last timepoints) during closed-center-open runsLinear mixed effects model timepoint mouse genotype timept X genotype0.085
0.16
0.0044
0.010
673937
Figure 4EFSIN chargeWilcoxon rank sum0.00663117
Figure 4FFSIN PPRWilcoxon rank sum0.0363117
Figure 4GFSIN latencyWilcoxon rank sum0.01363117
Figure 4HFSIN # spikesWilcoxon rank sum0.0863117
Figure 5EPyr chargeWilcoxon rank sum0.281381711
Figure 5FPyr PPRWilcoxon rank sum0.151381711
Figure 5GPyr latencyWilcoxon rank sum0.761381711
Figure 5HPyr # spikesWilcoxon rank sum0.781381711
Figure 1—figure supplement 1Sex-corrected zone occupancyWilcoxon rank sum0.0131827
Figure 1—figure supplement 1AZone occupancy for Het M vs. FWilcoxon rank sum0.60M: 10, F: 17
Figure 1—figure supplement 1BSex-corrected EPM distanceWilcoxon rank sum0.791623
Figure 1—figure supplement 1CHead dips: genotype2-way ANOVA0.02M: 10, F: 4M: 8, F: 6
Figure 1—figure supplement 1CHead dips: sex2-way ANOVA0.81M: 10, F: 4M: 8, F: 6
Figure 1—figure supplement 1CHead dips: genotype X sex2-way ANOVA0.36M: 10, F: 4M: 8, F: 6
Figure 1—figure supplement 1CHead dips for Het M vs. FWilcoxon rank sum0.54M: 8, F: 6
Figure 1—figure supplement 1DOpen arm entries: genotype2-way ANOVA0.22M: 12, F: 4M: 9, F: 14
Figure 1—figure supplement 1DOpen arm entries: sex2-way ANOVA0.61M: 12, F: 4M: 9, F: 14
Figure 1—figure supplement 1DOpen entries: genotype X sex2-way ANOVA0.32M: 12, F: 4M: 9, F: 14
Figure 1—figure supplement 1EOpen visit length: genotype2-way ANOVA0.22M: 12, F: 4M: 9, F: 14
Figure 1—figure supplement 1EOpen visit length: sex2-way ANOVA0.49M: 12, F: 4M: 9, F: 14
Figure 1—figure supplement 1EOpen visit length: genotype X sex2-way ANOVA0.76M: 12, F: 4M: 9, F: 14
Figure 1—figure supplement 1FSex-corrected open arm timeWilcoxon rank sum0.0131623
Figure 1—figure supplement 1FOpen arm time: Het M vs. FWilcoxon rank sum0.61M: 10, F: 17
Figure 1—figure supplement 1GCenter time: genotype2-way ANOVA0.087M: 12, F: 6M: 10, F: 17
Figure 1—figure supplement 1GCenter time: sex2-way ANOVA0.29M: 12, F: 6M: 10, F: 17
Figure 1—figure supplement 1GCenter time: genotype X sex2-way ANOVA0.48M: 12, F: 6M: 10, F: 17
Figure 1—figure supplement 2ASocial interactionWilcoxon rank sum0.3477
Figure 1—figure supplement 2BNovel objectionWilcoxon rank sum0.9577
Figure 1—figure supplement 2CMarble buryingWilcoxon rank sum0.4587
Figure 1—figure supplement 2DOF distanceWilcoxon rank sum0.151417
Figure 1—figure supplement 2FT-maze trialsWilcoxon rank sum0.655
Figure 1—figure supplement 2HRule shift IAWilcoxon rank sum0.8944
Figure 1—figure supplement 2HRule shift RSWilcoxon rank sum0.8944
Figure 2—figure supplement 1APFC theta powerWilcoxon rank sum0.9167
Figure 2—figure supplement 1APFC beta powerWilcoxon rank sum0.9467
Figure 2—figure supplement 1APFC low gamma powerWilcoxon rank sum0.4767
Figure 2—figure supplement 1APFC high gamma powerWilcoxon rank sum0.867
Figure 2—figure supplement 1BHPC Theta powerWilcoxon rank sum0.2367
Figure 2—figure supplement 1BHPC Beta powerWilcoxon rank sum0.09367
Figure 2—figure supplement 1BHPC low gamma powerWilcoxon rank sum0.1767
Figure 2—figure supplement 1BHPC high gamma powerWilcoxon rank sum0.9467
Figure 2—figure supplement 1CPFC closed theta powerWilcoxon rank sum0.8867
Figure 2—figure supplement 1CPFC closed beta powerWilcoxon rank sum167
Figure 2—figure supplement 1CPFC closed LG powerWilcoxon rank sum0.2967
Figure 2—figure supplement 1CPFC closed HG powerWilcoxon rank sum0.167
Figure 2—figure supplement 1DHPC closed theta powerWilcoxon rank sum0.2567
Figure 2—figure supplement 1DHPC closed beta powerWilcoxon rank sum0.1567
Figure 2—figure supplement 1DHPC closed LG powerWilcoxon rank sum0.4867
Figure 2—figure supplement 1DHPC closed HG powerWilcoxon rank sum0.8967
Figure 2—figure supplement 1EPFC open theta powerWilcoxon rank sum0.8967
Figure 2—figure supplement 1EPFC open beta powerWilcoxon rank sum0.8967
Figure 2—figure supplement 1EPFC open LG powerWilcoxon rank sum167
Figure 2—figure supplement 1EPFC open HG powerWilcoxon rank sum0.1567
Figure 2—figure supplement 1FHPC open theta powerWilcoxon rank sum0.3267
Figure 2—figure supplement 1FHPC open beta powerWilcoxon rank sum0.267
Figure 2—figure supplement 1FHPC open LG powerWilcoxon rank sum0.2567
Figure 2—figure supplement 1FHPC open HG powerWilcoxon rank sum167
Figure 3—figure supplement 1DIC #1 zone projectionWilcoxon rank sum0.007673937
Figure 3—figure supplement 1DIC #1 zone projection t = 0 vs. baseline (average of first and last timepoints) during closed-center-open runsLinear mixed effects model timepoint mouse genotype timept X genotype0.085
0.16
0.0044
0.010
673937
Figure 3—figure supplement 1FIC #3 zone projectionWilcoxon rank sum0.015673937
Figure 3—figure supplement 1FIC #3 zone projection t = 0 vs. baseline (average of first and last timepoints) during closed-center-open runsLinear mixed effects model timepoint mouse genotype timept X genotype0.0094
0.50
0.026
0.052
673937
Figure 4—figure supplement 1CFSIN resting potentialWilcoxon rank sum0.5063117
Figure 4—figure supplement 1DFSIN input resistanceWilcoxon rank sum0.4463117
Figure 4—figure supplement 1EFSIN halfwidthWilcoxon rank sum0.4763117
Figure 4—figure supplement 1FFSIN max firing rateWilcoxon rank sum0.5063117
Figure 5—figure supplement 1CPyr resting potentialWilcoxon rank sum0.941381711
Figure 5—figure supplement 1DPyr input resistanceWilcoxon rank sum0.801381711
Figure 5—figure supplement 1EPyr halfwidthWilcoxon rank sum0.461381711
Figure 5—figure supplement 1FPyr max firing rateWilcoxon rank sum0.931381711

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