Inactive but awake behaviour as indicating a depression-like state in mice: Aetiological factors and association with adult hippocampal neurogenesis
Data files
Oct 03, 2025 version files 157.70 KB
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Final_code_All_Observations_Absolute_values_Figure_5.R
4.50 KB
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Proportion_of_time_spent_IBA_during_Observation_1.xlsx
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Proportion_of_time_spent_IBA_while_visible_all_obs_Figure_5.xlsx
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Proportion_of_time_spent_IBA_while_visible_change_between_obs_1-2.xlsx
13.86 KB
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Proportion_of_time_spent_IBA_while_visible_change_between_obs_1-3.xlsx
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Proportion_of_time_spent_IBA_while_visible_change_between_obs_2-3.xlsx
13.87 KB
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Proportion_of_time_spent_IBA_while_visible_obs_3_plus_cells_per_mm_in_vDG_and_dDG.xlsx
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README.md
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Trevarthen_et_al_All_data.xlsx
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Trevarthen_et_al_Final_code_to_analyse_change_in_IBA_between_Observations_1_and_2.R
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Trevarthen_et_al_Final_code_to_analyse_change_in_IBA_between_Observations_1_and_3.R
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Trevarthen_et_al_Final_code_to_analyse_change_in_IBA_between_Observations_2_and_3.R
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Trevarthen_et_al_Final_code_to_analyse_vDG_dDG_and_IBA_obs_3.R
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Abstract
In laboratory mice, ‘inactive but awake’ (IBA) home-cage behaviour involves animals being spontaneously motionless with eyes open, not interacting with their surroundings. Conventional (barren) housing typically triggers IBA more than comparatively enriched environments. Compellingly greater IBA is associated with some depression-like features in mice and we further explored this through three aims. First, we aimed to replicate previous results highlighting environmental and genetic (using two strains of mice: DBA/2J and C57BL/6J) aetiological contributors to IBA. Second, we explored whether the performance of IBA varied as the level of enrichment was either increased or reduced. Third, we opportunistically investigated whether elevated IBA predicted lower density of immature neurons in the dorsal (dDG) or ventral dentate gyrus (vDG) of the hippocampus. As expected, mice housed in conventional cages displayed more IBA than those in comparatively enriched cages and even more so in DBA/2J mice. As predicted enrichment loss generally increased IBA while enrichment gain decreased IBA. Unsurprisingly, immature neuron density was lower in conventional compared to enriched cages, although only for vDG. Elevated IBA predicted reduced immature neuron density in the dDG, and this effect tended to be stronger for C57BL/6Js.
Dataset DOI: 10.5061/dryad.8cz8w9h59
Description of the data and file structure
Animals, housing and husbandry
Thirty-one female C57BL/6J (C57, hereafter) and 31 female DBA/2J (DBA, hereafter) mice were pair-housed post-weaning in either highly enriched (N = 15 cages) or non-enriched (N = 16 cages) transparent Techniplast cages.
Behavioural scan sampling of mice
The behaviour relevant to the hypothesis under test was being inactive but awake (IBA hereafter), defined as ‘mouse motionless, muzzle in sight and eyes open, for at least 15s’. All observations were conducted during the animals’ dark (active) phase under red ambient light, for three weeks, four days per week, over four 90-minute time blocks per day: 9:30-11:00, 11:30-13:00, 13:45-15:15, 15:45-17:15. Behaviour was recorded via live scan-sampling, switching from scan to 15s focal sampling to allow for differentiation between behaviours characterised by a lack of movement (e.g. IBA versus sleeping). In total, 24 scan samples were taken per mouse each day, spread evenly across the four blocks (totalling 288 scan samples/mouse for this first phase of observation (IBA Observation 1, Pre-adjustment Phase)).
Environmental adjustment, i.e. moving into the alternative environment, or staying in the initial environment for control groups, happened on the day following the last day of observation in the Pre-adjustment Phase. Home-cage behaviour was monitored again for three consecutive weeks starting 2 days after environmental adjustment (IBA Observation 2, Post-adjustment Phase), following the above-described procedure and also totalling 288 scan samples/mouse during this second phase of observation. Finally, we had the opportunity to observe IBA in the mice during the 8th week following environmental adjustment (IBA Observation 3, Post-adjustment Phase). This followed the procedure outlined for Observations 1 and 2 with the exception that behavioural observations took place over one week instead of three, totalling 96 scan samples/mouse during this observation. In the attached data files, the overall mean proportion of visible scans spent performing IBA has been calculated for each observation period.
When analysing the change in IBA between observations, the change in mean IBA has been calculated.
We also present the immature neuron density in the dorsal (dDG) and ventral (vDG) regions of the dentate gyrus in the hippocampus for each mouse (alongside its IBA during observation 3).
Files and variables
File: Final_code_All_Observations_Absolute_values_Figure_5.R
Description: The R script code used to analyse the mean proportion of visible time each mouse spent performing IBA during each of the 3 observation periods and to generate Figure 5 in the manuscript.
File: Proportion_of_time_spent_IBA_during_Observation_1.xlsx
Description: The data used to analyse the mean proportion of visible time each mouse spent performing IBA during observation 1.
Variables
- Mouse Unique Individual Mouse ID (range 1-62 mice)
- Cage Individual Cage ID (range 1-31 mice)
- Strain Strain of mouse: DBA = DBA/2J; C57 = C57BL/6J. One of each strain was housed in each cage
- Ttm Treatment: NE (housed initially in non-enriched condition i.e. for observation 1); EE (housed initially in enriched condition i.e. for observation 1)
- IBA Proportion of visible scans the mouse spent displaying Inactive but awake (IBA) behaviour during observation 1
File: Proportion_of_time_spent_IBA_while_visible_all_obs_Figure_5.xlsx
Description: The data used to analyse the mean proportion of visible time each mouse spent performing IBA during each of the 3 observation periods and to generate Figure 5 in the manuscript.
Variables
- Mouse Unique Individual Mouse ID (range 1-62 mice)
- Cage Individual Cage ID (range 1-31 mice)
- Strain Strain of mouse: DBA = DBA/2J; C57 = C57BL/6J. One of each strain was housed in each cage
- Observation a=Observation 1 (Days 4-22: During the first 3 weeks of housing following a 3 day acclimatisation); b=Observation 2 (Days 25-41: During the 3 weeks immediately following the environmental adjustment, where the environment was adjusted); c=Observation 3 (Days 74-79: During the 8th week following the environmental adjustment)
- Ttm Treatment: NE-NE (stably housed in non-enriched condition throughout experiment); EE-EE (stably housed in enriched condition throughout the experiment); NE-EE (started in the non-enriched condition and moved to the enriched housing when the environmental adjustment occurred); EE-NE (started in the enriched condition and moved to the non-enriched housing when the environmental adjustment occurred)
- IBA Proportion of visible scans the mouse spent displaying Inactive but awake (IBA) behaviour
File: Proportion_of_time_spent_IBA_while_visible_obs_3_plus_cells_per_mm_in_vDG_and_dDG.xlsx
Description: The data used to analyse the association between the mean proportion of visible time each mouse spent performing IBA during observation 3 and the immature neuron density (cells/mm) in the ventral (vDG) and dorsal (dDG) regions of the dentate gyrus in the hippocampus.
Variables
- Mouse Unique Individual Mouse ID (range 1-62 mice)
- Cage Individual Cage ID (range 1-31 mice)
- Strain Strain of mouse: DBA = DBA/2J; C57 = C57BL/6J. One of each strain was housed in each cage
- Ttm Treatment: NE-NE (stably housed in non-enriched condition throughout experiment); EE-EE (stably housed in enriched condition throughout the experiment)
- IBA Proportion of visible scans the mouse spent displaying Inactive but awake (IBA) behaviour during observation 3
- Dorsal Cells per mm in the Dorsal region of the dentate gyrus in the hippocampus. Measure taken at end of life.
- Ventral Cells per mm in the Ventral region of the dentate gyrus in the hippocampus. Measure taken at end of life.
File: Proportion_of_time_spent_IBA_while_visible_change_between_obs_1-2.xlsx
Description: The data used to analyse the change in the mean proportion of visible time each mouse spent performing IBA between observations 1 and 2.
Variables
- Mouse Unique Individual Mouse ID (range 1-62 mice)
- Cage Individual Cage ID (range 1-31 mice)
- Strain Strain of mouse: DBA = DBA/2J; C57 = C57BL/6J. One of each strain was housed in each cage
- Ttm Treatment: NE-NE (stably housed in non-enriched condition throughout experiment); EE-EE (stably housed in enriched condition throughout the experiment); NE-EE (started in the non-enriched condition and moved to the enriched housing when the environmental adjustment occurred); EE-NE (started in the enriched condition and moved to the non-enriched housing when the environmental adjustment occurred)
- IBA Proportion of visible scans the mouse spent displaying Inactive but awake (IBA) behaviour
File: Proportion_of_time_spent_IBA_while_visible_change_between_obs_2-3.xlsx
Description: The data used to analyse the change in the mean proportion of visible time each mouse spent performing IBA between observations 2 and 3.
Variables
- Mouse Unique Individual Mouse ID (range 1-62 mice)
- Cage Individual Cage ID (range 1-31 mice)
- Strain Strain of mouse: DBA = DBA/2J; C57 = C57BL/6J. One of each strain was housed in each cage
- Ttm Treatment: NE-NE (stably housed in non-enriched condition throughout experiment); EE-EE (stably housed in enriched condition throughout the experiment); NE-EE (started in the non-enriched condition and moved to the enriched housing when the environmental adjustment occurred); EE-NE (started in the enriched condition and moved to the non-enriched housing when the environmental adjustment occurred)
- IBA Proportion of visible scans the mouse spent displaying Inactive but awake (IBA) behaviour
File: Proportion_of_time_spent_IBA_while_visible_change_between_obs_1-3.xlsx
Description: The data used to analyse the change in the mean proportion of visible time each mouse spent performing IBA between observations 1 and 3.
Variables
- Mouse Unique Individual Mouse ID (range 1-62 mice)
- Cage Individual Cage ID (range 1-31 mice)
- Strain Strain of mouse: DBA = DBA/2J; C57 = C57BL/6J. One of each strain was housed in each cage
- Ttm Treatment: NE-NE (stably housed in non-enriched condition throughout experiment); EE-EE (stably housed in enriched condition throughout the experiment); NE-EE (started in the non-enriched condition and moved to the enriched housing when the environmental adjustment occurred); EE-NE (started in the enriched condition and moved to the non-enriched housing when the environmental adjustment occurred)
- IBA Proportion of visible scans the mouse spent displaying Inactive but awake (IBA) behaviour
File: Trevarthen_et_al_All_data.xlsx
Description: All data included in all analyses
Variables
- Mouse Unique Individual Mouse ID (range 1-62 mice)
- Cage Individual Cage ID (range 1-31 mice)
- Strain Strain of mouse: DBA = DBA/2J; C57 = C57BL/6J. One of each strain was housed in each cage
- Ttm Treatment: NE-NE (stably housed in non-enriched condition throughout experiment); EE-EE (stably housed in enriched condition throughout the experiment); NE-EE (started in the non-enriched condition and moved to the enriched housing when the environmental adjustment occurred); EE-NE (started in the enriched condition and moved to the non-enriched housing when the environmental adjustment occurred)
- IBA Proportion of visible scans the mouse spent displaying Inactive but awake (IBA) behaviour during observation 3
- Dorsal Cells per mm in the Dorsal region of the dentate gyrus in the hippocampus. Measure taken at end of life.
- Ventral Cells per mm in the Ventral region of the dentate gyrus in the hippocampus. Measure taken at end of life.
File: Trevarthen_et_al_Final_code_to_analyse_change_in_IBA_between_Observations_1_and_2.R
Description: The R script file and code used to analyse the change in the mean proportion of visible time each mouse spent performing IBA between observations 1 and 2.
File: Trevarthen_et_al_Final_code_to_analyse_change_in_IBA_between_Observations_1_and_3.R
Description: The R script file and code used to analyse the change in the mean proportion of visible time each mouse spent performing IBA between observations 1 and 3.
File: Trevarthen_et_al_Final_code_to_analyse_vDG_dDG_and_IBA_obs_3.R
Description: The R script file and code used to analyse the association between the mean proportion of visible time each mouse spent performing IBA during observation 3 and the immature neuron density (cells/mm) in the ventral (vDG) and dorsal (dDG) regions of the dentate gyrus in the hippocampus.
File: Trevarthen_et_al_Final_code_to_analyse_change_in_IBA_between_Observations_2_and_3.R
Description: The R script file and code used to analyse the change in the mean proportion of visible time each mouse spent performing IBA between observations 2 and 3.
Code/software
R Studio required
install.packages("readr")
install.packages("multcomp")
install.packages("emmeans")
install.packages("scales")
install.packages("ggExtra")
install.packages("ggsignif")
install.packages("nlme")
install.packages("lme")
install.packages(lme4)
install.packages(ggplot2)
install.packages(dplyr)
install.packages(MASS)
install.packages(multcomp)
install.packages(emmeans)
install.packages("statmod")
install.packages("tweedie")
install.packages("lsmeans")
install.packages("nlme")
install.packages(scales)
install.packages(stringr)
install.packages('ggExtra')
install.packages("ggsignif")
install.packages("effectsize")