home cage activity
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2022 ◽  
Vol 15 ◽  
Author(s):  
Laura C. E. Steel ◽  
Selma Tir ◽  
Shu K. E. Tam ◽  
James N. Bussell ◽  
Manuel Spitschan ◽  
...  

Light is known to exert powerful effects on behavior and physiology, including upon the amount and distribution of activity across the day/night cycle. Here we use home cage activity monitoring to measure the effect of differences in home cage light spectrum and intensity on key circadian activity parameters in mice. Due to the relative positioning of any individually ventilated cage (IVC) with regard to the animal facility lighting, notable differences in light intensity occur across the IVC rack. Although all mice were found to be entrained, significant differences in the timing of activity onset and differences in activity levels were found between mice housed in standard versus red filtering cages. Furthermore, by calculating the effective irradiance based upon the known mouse photopigments, a significant relationship between light intensity and key circadian parameters are shown. Perhaps unsurprisingly given the important role of the circadian photopigment melanopsin in circadian entrainment, melanopic illuminance is shown to correlate more strongly with key circadian activity parameters than photopic lux. Collectively, our results suggest that differences in light intensity may reflect an uncharacterized source of variation in laboratory rodent research, with potential consequences for reproducibility. Room design and layout vary within and between facilities, and caging design and lighting location relative to cage position can be highly variable. We suggest that cage position should be factored into experimental design, and wherever possible, experimental lighting conditions should be characterized as a way of accounting for this source of variation.


Author(s):  
Kseniya P. Avimova ◽  
Dmitry B. Sandakov

Laboratory animals often develop abnormal repetitive (stereotypic) behaviour that can influence both physiology and behavioural test results. Such abnormal behaviours usually develop in suboptimal environment and increase over time. To explore the development of stereotypic forms of activity night home-cage behaviour of laboratory mice was analysed and collated with the behaviour in open field (OFT), hole-board (HBT) and tail suspension (TST) tests twice within 16 weeks. Mice expressed few stereotypies and their duration lessened over time from median 8.2 to 1.0 %. In contrast, grooming behaviour increased significantly from 29.5 to 49.6 %. Home-cage grooming correlated with the latency of locomotion start in OFT and with the immobility time in TST. Intensity and stability of stereotypic activity and grooming inf­luenced the duration of grooming in OFT: the mice with unstable stereotypies groomed more than others, and mice with the lowes home-cage grooming level also groomed in OFT the most. Intensity and stability of night grooming influenced the behaviour in TST: the mice with unstable level of grooming were the most mobile in this test. Abnormal home-cage activity may indicate impaired welfare, and that, in turn, may affect test activity, so researchers need to keep it in mind when planning animal behaviour experiments.  


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A232-A232
Author(s):  
Ruben Rodriguez ◽  
Candice B Herber ◽  
William C Krause ◽  
Holly A Ingraham

Abstract Loss of peripheral estrogen in postmenopausal women is often associated with decreased physical activity and loss of bone mass, leading to an increased risk of metabolic diseases, osteoporosis, and skeletal fragility. While it is well-established that loss of peripheral estrogen signaling results in bone loss, we previously found that eliminating central estrogen signaling paradoxically results in an unexpected massive increase in bone mass only in female mice. Specifically, deletion of estrogen receptor alpha (ERα) signaling in kisspeptin 1 (Kiss1) expressing neurons of the arcuate nucleus (ARCKiss1) increases bone mass at the expense of reproduction in female mice. Currently, the mechanisms and the neurocircuits that modulate these unexpected responses are unknown. Here, to begin addressing these questions, we asked if changing the neuronal output of ARCKiss1 neurons using chemogenetic manipulation of ARCKiss1 neurons might also alter bone mass and locomotion in female mice. To do this, we delivered stimulatory (AAV2-hM3Dq-mCherry) designer receptors exclusively activated by designer drugs (DREADDs) to the ARC of wild type and Kiss1-Cre+ (Kiss1-CrehM3q-DREADDs) female mice and asked if chronic activation of ARCKiss1 neurons might alter bone mass as analyzed by standard ex-vivo µCT imaging. Clozapine N-oxide (CNO) was delivered for 22 days (0.1 mg/mL). We also leveraged the ANY-Maze system to assess home cage activity over an extensive 96-hour period. Acute activation of ARCKiss1 tended to decrease home cage activity by nearly 40% in Kiss1-CrehM3q-DREADDs mice during the dark period compared to WT females. Interestingly, chronic activation of ARCKiss1 neurons significantly lowered trabecular bone volume by nearly 30%. Current studies are underway to ask if inhibiting ARCKiss1 neurons results in increased bone mass. Our findings collectively suggest that the neuronal activity of ARCKiss1 neurons is sufficient to shift energy allocation away from locomotion and bone-building to maximize reproductive capacity. We speculate that the widely used SERM in breast cancer treatment, Tamoxifen, might exert its bone sparing effect by silencing ARCKiss1 neurons.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Karin Pernold ◽  
Eric Rullman ◽  
Brun Ulfhake

AbstractThe mouse is the most important mammalian model in life science research and the behavior of the mouse is a key read-out of experimental interventions and genetic manipulations. To serve this purpose a solid understanding of the mouse normal behavior is a prerequisite. Using 14–19 months of cumulative 24/7 home-cage activity recorded with a non-intrusive technique, evidence is here provided for a highly significant circannual oscillation in spontaneous activity (1–2 SD of the mean, on average 65% higher during peak of highs than lows; P = 7E−50) of male and female C57BL/6 mice held under constant conditions. The periodicity of this hitherto not recognized oscillation is in the range of 2–4 months (average estimate was 97 days across cohorts of cages). It off-sets responses to environmental stimuli and co-varies with the feeding behavior but does not significantly alter the preference for being active during the dark hours. The absence of coordination of this rhythmicity between cages with mice or seasons of the year suggest that the oscillation of physical activity is generated by a free-running intrinsic oscillator devoid of external timer. Due to the magnitude of this rhythmic variation it may be a serious confounder in experiments on mice if left unrecognized.


2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Hiroshi Ueno ◽  
Shunsuke Suemitsu ◽  
Shinji Murakami ◽  
Naoya Kitamura ◽  
Kenta Wani ◽  
...  

Background. Although population housing is recommended by many animal management and ethical guidelines, the effect of collective housing of mice of different age groups on mouse behavior has not been clarified. Since the development of the central nervous system continues to occur before sexual maturation, the stress of social ranking formation among male individuals in mixed housing conditions can affect postmaturation behavior. To assess these effects, sexually immature mice of different ages were housed in the same cage and a series of behavioral tests were performed after maturation. Results. The findings for three groups of mice—junior mice housed with older mice, senior mice housed with younger mice, and mice housed with other mice of the same age—were compared. Junior mice showed higher body weight and activity as well as lower grip strength and anxiety-like behaviors than other mice. In contrast, senior mice showed lower body temperature and increased aggression, antinociceptive effect, and home-cage activity in the dark period in comparison with other mice. Conclusions. Thus, combined housing of immature mice of different age groups affects mouse behavior after maturation. Appropriate prematuration housing conditions are crucial to eliminate the uncontrollable bias caused by age-related social stratification.


2020 ◽  
Author(s):  
K. Pernold ◽  
E. Rullman ◽  
B. Ulfhake

AbstractUsing 14-20 months of cumulative 24/7 home-cage activity recorded with a non-intrusive technique and a data driven analytical approach, we here provide evidence for the existence of a circannual oscillation (1-2 SD of the mean, on average 65% higher during peak of highs than lows; P=7E-50) in spontaneous activity of male and female C57BL/6 mice held under constant barrier conditions (dark-light cycle 12/12 h (DL), temperature 21±1°C, humidity 40-60%). The periodicity of the season-like oscillation is in the range of 2-4 months (on average 97 days across cohorts of cages) and off-sets also responses to environmental stimuli but does not significantly alter the preference for activity during the dark hours of this nocturnal mouse strain (P=0.11 difference between highs and lows).The significance of this hitherto not recognized slow rhythmic alteration in spontaneous activity is further substantiated by its co-variation with the feeding behaviour of the mice. The absence of coordination within and between cohorts of cages or synchronization to the seasons of the year, suggests that the oscillation of in-cage activity and behavioural responses is generated by a free-running intrinsic oscillator devoid of synchronization with an out-of-cage environmental time-keeper. Since the variation over time has such a magnitude and correlate with the feeding behaviour it is likely that it will impact a range of long term experiments conducted on laboratory mice if left unrecognized.


2019 ◽  
Author(s):  
Zach Dwyer ◽  
Chris Rudyk ◽  
Divya Situt ◽  
Sheryl Beauchamp ◽  
Jawaria Abdali ◽  
...  

Abstract Background: Substantial data have implicated microglial-driven neuroinflammation in Parkinson’s disease (PD) and environmental toxicants have been long expected as triggers of such inflammatory processes. Of course, these environmental insults act in the context of genetic vulnerability factors and in this regard, leucine rich repeat kinase 2 (LRRK2), may play a prominent role.Methods: We used a double hit, lipopolysaccharide (LPS; endotoxin) followed by paraquat (pesticide toxicant) model of PD in mice with the most common LRRK2 mutation G2019S, knockin mice and wild type littermates. In order to assess the contribution of microglia, we depleted these cells (through 14 days of the CSF-1 antagonist, PLX-3397) prior to LPS and paraquat exposure.Results: We found that the G2019S mice displayed the greatest signs of behavioral pathology, but that the PLX-3397 induced microglial depletion at the time of LPS exposure diminished toxicity and weight loss and blunted the reduction in home-cage activity with subsequent paraquat exposure. However, neither the PLX-3397 pre-treatment nor the G2019S mutation affected the LPS + paraquat induced loss of substantia nigra pars compacta (SNc) dopamine neurons or elevation of circulating immune (IL-6) or stress (corticosterone) factors. Intriguingly, microglial morphological ratings were basally enhanced in G2019S mice and the PLX-3397 pre-treatment reversed this effect. Moreover, PLX-3397 pre-treatment selectively elevated soluble a-synuclein and SIRT3 levels, while reducing SNc caspase-1 and 3, along with CX3CR1. Hence, the re-populated “new” microglia following cessation of PLX-3397 clearly had an altered phenotype or were immature at the time of sacrifice (i.e. after 11 days).Conclusions: Collectively, these findings suggest that G2019S knock-in and PLX-3397 microglial depletion at the time of LPS exposure affects behavioral, but not neurodegenerative responses to subsequent environmental toxin exposure.


2019 ◽  
Vol 38 (5) ◽  
pp. 339-356 ◽  
Author(s):  
David V. Gauvin ◽  
Zachary J. Zimmermann ◽  
Jill A. Dalton ◽  
Theodore J. Baird ◽  
Mary-Jeanne Kallman

In the adoption of behavior as a critical end point in safety pharmacology and neurotoxicity screening, federal regulatory agencies have shifted the predominating scientific perspective from pharmacology back to the experimental analysis of behavior (psychology). Nowhere is this more evident than in tier I safety assessment of the central nervous system (CNS). The CNS and peripheral nervous system have multiple behavioral units of general activity. A complete picture of the motor control neural pathways cannot be measured by any one single approach. The CNS safety protocols under International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use S7A are required to be conducted in accordance with Good Laboratory Practices by trained technical staff. The CNS safety assessments necessitate the inclusion of a thorough and detailed behavioral analysis of home cage activity, the response to handling, and transportation to and observations within an open-field apparatus with ancillary measures of basal muscle tone, muscle strength, and tremor in a functional observation battery, as well as quantitative measurements of 3-dimensional activity in an automated photobeam arena. Cost-cutting initiatives or a radical application of the “reduce use” principle of the 3 Rs only jeopardize the spirit, intent, and predictive validity of tier I safety testing assays dictated by current drug safety guidelines.


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