Data and code from: Early spatial and contextual coding deficits in hippocampal CA1 precede performance decline in an Alzheimer’s disease model
Data files
Sep 28, 2026 version files 44.06 MB
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Dryad_dataset.zip
44.06 MB
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README.md
8.56 KB
Abstract
Alzheimer’s disease (AD) is characterized by progressive memory decline, yet how hippocampal representations change at early AD stages remains largely unknown. In this study, we utilized a real-world head-fixed spatial alternation task combined with in vivo two-photon imaging to investigate hippocampal CA1 representations in 5xFAD mice. While 7-9 month old 5xFAD mice showed significant deficits in task learning, 2-4 month old mice performed normally, enabling assessment of hippocampal coding prior to behavioral decline. At this early stage, CA1 neurons exhibited intact global spatial encoding but demonstrated impaired task-related place cell representations. Contextual representations revealed by trajectory-dependent coding were weakened at both the population and single cell levels, accompanied by a notable shift from predominantly retrospective to more prospective encoding during behavioral choices. During task learning, longitudinally unstable place cells showed greater impairments in spatial coding, whereas stable place cells remained largely preserved in early-stage AD mice. Additionally, chemogenetic activation of basal forebrain cholinergic neurons increased spatial information and within-session stability, while promoting trajectory-dependent coding in these early-stage 5xFAD mice. Together, these findings reveal selective early impairments in hippocampal task-related spatial and contextual representations in AD that precede overt deficits in spatial alternation performance and remains amenable to cholinergic modulation. This dataset contains data and code sufficient to reconstruct certain figures of the paper, and to allow for subsequent further analyses.
Overview
This deposit contains the processed data and MATLAB code used to generate the main figures and statistical analyses in the associated manuscript. It also includes representative behavior trajectories and calcium imaging time series used for the Figure 1 examples.
The figure workbooks contain the final numerical inputs used by the plotting scripts. They are processed data rather than raw microscopy movies or raw acquisition files.
Directory structure
Dryad_dataset/
|-- README.md
|-- analysis_code/
| |-- Fig1/
| |-- Fig2/
| |-- Fig3/
| |-- Fig4/
| |-- Fig5/
| |-- Fig6/
| `-- useful_function/
| |-- box_violin_plot.m
| `-- plot_ROIwave.m
|-- figure_data/
| |-- figure_1.xlsx
| |-- figure_2.xlsx
| |-- figure_3.xlsx
| |-- figure_4.xlsx
| |-- figure_5.xlsx
| `-- figure_6.xlsx
|-- behavior_trajectory_example/
|-- calcium_timeseries_example/
Keep this directory structure unchanged. Each MATLAB script locates the dataset root from its own file path, so no user-specific absolute paths are required.
Figure data and analysis code
Each Excel workbook corresponds to one main figure. Worksheet names identify the panel or group of panels. MATLAB scripts are stored in the matching folder under analysis_code/.
Some worksheets contain more than one data block. These additional blocks hold values used for heatmaps, position-binned traces, or other panel-specific plots. The scripts read the required ranges directly.
Workbook and worksheet contents
figure_1.xlsx
- fig1_c: Amyloid-beta area coverage (%) in the total hippocampus, subiculum, CA1-CA3, and dentate gyrus at 3.5 and 7.5 months.
- fig1_e and fig1_h: Daily Phi-maze correct performance (%) in young and old Ctrl and AD mice, respectively.
- fig1_f and fig1_i: Block-level predicted correct performance (%) across trials in young and old mice, respectively.
- fig1_j_left and fig1_k_left: Cell-level spatial information (bits/arb) in young and old mice, respectively.
- fig1_j_right and fig1_k_right: Session-level place cell proportions (%) in young and old mice, respectively.
figure_2.xlsx
- Fig2_b: Imaging-session alternation performance (%) and mean correct-trial running speed (cm/s).
- Fig2_c: Cell-level spatial information of one-dimensional place cells (bits/arb).
- Fig2_d: Cell-level place-field peak activity (A.U.) and position-binned group means and SEM; position is in cm.
- Fig2_e: Cell-level place-field selectivity and position-binned group means and SEM; selectivity is dimensionless and position is in cm.
- Fig2_f: Population-vector correlation values and group correlation maps across maze positions; correlations are dimensionless and position is in cm.
- Fig2_g: Within-session tuning-curve correlation values and group correlation maps across maze positions; correlations are dimensionless and position is in cm.
- Fig2_h: Correct-trial correlation matrices for Ctrl and AD mice and the AD-minus-Ctrl difference matrix; values are correlation coefficients.
- Fig2_i: Mean trial-to-trial correlations for early, middle, and late trial windows; values are dimensionless correlation coefficients.
figure_3.xlsx
- Fig3_e: Counts and percentages of stable place cells across three recording stages.
- Fig3_f: Tuning-curve correlations of stable place cells between recording days; values are dimensionless correlation coefficients.
- Fig3_g: Trial-to-trial tuning-curve correlation, spatial information, place-field selectivity, and in-field peak activity of stable place cells across stages.
- Fig3_h: The same spatial-coding measures as Fig3_g for unstable place cells.
figure_4.xlsx
- Fig4_c: Mean activity rate (A.U./s) and SEM for high- and low-rate trajectories across stem position (cm).
- Fig4_d: Mean split probability and SEM across stem position (cm).
- Fig4_e: Session-level and position-binned LDA classification accuracy; accuracy is expressed as a fraction from 0 to 1.
- Fig4_f: Splitter-cell proportion (%) for each field of view.
- Fig4_g: Fraction of active trials classified as split trials for each splitter cell.
- Fig4_h: First trial on which significant splitting was detected for each splitter cell.
- Fig4_i: Split reliability (REL) for each splitter cell.
- Fig4_j: Split extent for each splitter cell.
- Fig4_k: Split discriminability (DIS) for each splitter cell.
figure_5.xlsx
- Fig5_d: Cell-level retrospective-prospective coding bias at each maze-position bin.
- Fig5_e: Mean retrospective-prospective coding bias for each cell.
- Fig5_f: Group mean and SEM of retrospective-prospective coding bias across maze positions (cm).
figure_6.xlsx
- Fig6_b: Phi-maze alternation performance (%) at session and mouse levels under saline and CNO conditions.
- Fig6_c: Cell-level global spatial information (bits/arb) under saline and CNO conditions.
- Fig6_d: Cell-level correct-trial spatial information (bits/arb) under saline and CNO conditions.
- Fig6_e-f: Cell-level trial-to-trial tuning-curve correlations and four group-by-condition correlation maps; correlation values are dimensionless and map positions are in cm.
- Fig6_g: Fraction of active trials classified as split trials for each cell under saline and CNO conditions.
- Fig6_h: First trial on which significant splitting was detected for each cell under saline and CNO conditions. NaN indicates that no significant split trial was identified.
The MATLAB scripts in analysis_code/Fig1 through analysis_code/Fig6 use the corresponding worksheets to reproduce the plots and statistical analyses.
Example MATLAB data files
Files in behavior_trajectory_example/ contain representative trajectories for young and old Ctrl and AD mice during early and final sessions. Variables x and y are maze coordinates, t is time in seconds, and Trial_ind identifies correct and incorrect trials.
calcium_timeseries_example/calcium_timeseries_example.mat contains representative raw fluorescence, delta-F/F, and deconvolved activity traces. Rows represent regions of interest and columns represent consecutive time samples spanning four minutes.
Abbreviations and units
AD, Alzheimer's disease-model (5xFAD) mice; Ctrl, control mice; A-beta, amyloid beta; HC, hippocampus; DG, dentate gyrus; ROI, region of interest; FOV, field of view; PC, place cell; PF, place field; PV, population vector; TC, tuning curve; SI, spatial information; LDA, linear discriminant analysis; CNO, clozapine-N-oxide; SEM, standard error of the mean; LR/RL, left-to-right/right-to-left running direction; REL, split reliability; DIS, split discriminability; A.U., arbitrary units.
Behavioral performance, area coverage, and cell proportions are reported as percentages. Position is reported in centimeters (cm), speed in centimeters per second (cm/s), activity rate in A.U./s, place-field peak activity in A.U., and spatial information in bits/arb. Correlation coefficients, selectivity, classification accuracy, probabilities, ratios, extent, discriminability, and retrospective-prospective bias are dimensionless. Time is reported in days, trials, seconds, or minutes as indicated by the variable or panel.
Missing values
In Fig6_h, rows are retained so that they correspond to the same cells in Fig6_g. A NaN in Fig6_h means that no first significant split trial could be assigned to that cell. The corresponding Fig6_g row contains a split-trial ratio of zero.
External software dependencies
Third-party MATLAB plotting code is not included in this dataset. Some figure-generation scripts (e.g. Figure 6) require the following external packages, which should be obtained separately from their original sources:
- DataViz (daboxplot): https://github.com/povilaskarvelis/DataViz
- shadedErrorBar: https://github.com/raacampbell/shadedErrorBar
- Violinplot-Matlab: https://github.com/bastibe/Violinplot-Matlab
- IoSR MATLAB Toolbox (multiwaveplot): https://github.com/IoSR-Surrey/MatlabToolbox
Citation and license
We encourage you to cite both the associated article and the Dryad dataset record when reusing these data or scripts. The persistent identifier, formal dataset citation, and dataset license are provided in the Dryad record.