Genetic factors and the measurement of exploratory activity

doi:10.1016/S0163-1047(87)90619-4

Behavioral and Neural Biology

Volume 48, Issue 1, July 1987, Pages 90-103

https://doi.org/10.1016/S0163-1047(87)90619-4 Get rights and content

The progenitor strains C57BL/6 and BALB/c and the seven recombinant inbred strains derived from them were used to examine the genetic relationship between two measures of activity and hippocampal lamination defect (Hld). Fifty-three mice (Mus musculus), 9 from each of the progenitor strains and 5 from each recombinant inbred strain, were tested for 16 min in a device which permitted both unobstructed traverse of the length of a runway and contact with objects which were aligned alongside the runway. The C57BL/6 mice produced significantly more locomotor (runway traversal) activity, whereas the BALB/c showed significantly greater amounts of investigatory (object contact) activity. This reversal of relative position in the distribution of scores was not present for the recombinant strains. There was no dichotomous separation of recombinant strains for either measure. Examination of activity in terms of four consecutive 4-min periods indicates differences among the strains with respect to changes during the test session. The strains may be dichotomized with respect to decrement in activity within the 16-min session, but these groups do not correspond with those reported by others. The inference of a single genetic determinant for activity measured either as locomotor or investigatory responses is not supported by these data, nor is there any apparent relationship between activity and Hid. The critical influence of genetic—environment interactions in determining behavior and the effect of the selection of measurement techniques upon interpretation of data are emphasized by these data.

References (20)

HendersonN.D.
Prior treatment effects on open field behaviour of mice—A genetic analysis
Animal Behaviour
(1967)
MoissetB.
Factors contributing to the modulation of norepinephrine uptake by synaptosomes from mouse brain cortex
Brain Research
(1977)
OliverioA.
Uses of recombinant inbred strains
OliverioA. et al.
Exploratory activity: Genetic analysis of its modification by scopolomine and amphetamine
Physiology and Behavior
(1973)
OliverioA. et al.
A gene influencing active avoidance performance in mice
Physiology and Behavior
(1973)
OliverioA. et al.
An analysis of single-gene effects on avoidance, maze, wheel running, and exploratory behavior in the mouse
Behavioral Biology
(1973)
van AbeelenJ.H.F.
Rearing responses and locomotor activity in mice: Singlelocus control
Behaviorial Biology
(1977)
van AbeelenJ.H.F.
Genetic analysis of locomotor activity in immature mice from two inbred strains
Behavioral Biology
(1979)
BaileyD.W.
Recombinant-inbred strains
BaileyD.W.
Recombinant inbred strains and bilineal congenic strains

There are more references available in the full text version of this article.

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Citation Excerpt :
The results of this study must be considered within the context of the behavioral traits and genetic background of C57Bl/6J mice. Substrains of C57 mice are relatively nonemotional, more active, and less aggressive than other inbred strains (BALB/c, DBA/2, C3H/He) with corresponding neurotransmitter phenotypes and differences in their stress responses (Cabib et al., 2002; Kempf et al., 1984; Kopp et al., 1999; Lalonde and Strazielle, 2008; Oliverio et al., 1973; Peeler and Nowakowski, 1987; Simler et al., 1982; van der Veen et al., 2007). In contrast to outbred (Swiss-Webster, Swiss CD-1) or wild mice, they show less basal, anxiety-related, or exploratory activities, less aggression, and more risk assessment (Hsieh et al., 2017; Parmigiani et al., 1999; Rodgers et al., 2002).
For basic research, rodents are often housed in individual cages prior to behavioral testing. However, aspects of the experimental design, such as duration of isolation and timing of animal manipulation, may unintentionally introduce variance into collected data. Thus, we examined temporal correlates of acclimation of C57Bl/6J mice to single housing in a novel environment following two commonly used experimental time periods (7 or 14 days, SH7 or SH14). We measured circulating stress hormones (adrenocorticotropic hormone and corticosterone), basally or after injection stress, hippocampal gene expression of transcripts implicated in stress and affect regulation: the glucocorticoid receptor (GR), the mineralocorticoid receptor (MR), including the MR/GR ratio, and fibroblast growth factor 2 (FGF2). We also measured signaling in the mammalian target of rapamycin (mTOR) pathway. The basal elevation of stress hormones in the SH14 group is accompanied by a blunting in the circadian rhythms of GR and FGF2 hippocampal gene expression, and the MR/GR ratio, that is observed in SH7 mice. Following mild stress, the endocrine response and hippocampal mTOR pathway signaling are decreased in the SH14 mice. These neural and endocrine changes at 14 days of single housing likely underlie increased anxiety-like behavior measured in an elevated plus maze test. We conclude that multiple measures of stress responsiveness change dynamically between one and two weeks of single housing. The ramifications of these alterations should be considered when designing animal experiments since such hidden sources of variance might cause lack of replicability and misinterpretation of data.
Species-relevant inescapable stress differently influences memory consolidation and retrieval of mice in a spatial radial arm maze
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And again, enhanced spatial memory performance of stressed rats was significantly correlated with their stress-induced serum corticosterone levels following an inverted-U-shape dose–response relationship [32,33,68,35]. Discussing results of studies using different subjects together, we have to emphasize that there are pronounced differences in behavioural and autonomic responses between rats and mice, as well as between different mice-strains in response to stress [45,62,21,4]. Moreover, studies indicating sex differences in learning during stressful times, while acute stress enhanced learning in male rats it was shown to impair learning in females [65,22,73,44,5].
Stress affects learning and there are both facilitating and impairing actions of stressors on memory processes. Here we investigated the influence of acute exposure to 2,5-dihydro-2,4,5-trimethylthiazoline (TMT), an ethological relevant stressor for rodents, on spatial memory formation and performance in a radial arm maze (RAM) task and studied TMT effects on corticosterone levels in GAD67-GFP knock-in mice and their wildtype littermates. Our results suggest that predator odor-exposure differently affects consolidation and retrieval of memory in a hippocampus-dependent spatial learning task in adult male mice, independently from their genotypes. Acute TMT-stress before retrieval facilitates performance, whereas repeated TMT-stress during consolidation exerts no influence. Additionally, we found genotype specific effects of TMT on corticosterone release. While TMT-stress tend to result in increased corticosterone release in wildtypes there was a significant decrease in transgenic mice.
Taken together, these findings indicate that biologically significant predator odor-induced stress can have different actions on the strength of spatial memory formation depending on the timing with regard to memory phases. Furthermore, we suppose an impact of GABAergic mechanisms on HPA-stress axis activation to TMT resulting in absent peripheral corticosterone release of GAD67-GFP mice.
Experiential and genetic contributions to depressive- and anxiety-like disorders: Clinical and experimental studies
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Stressful events have been implicated in the precipitation of depression and anxiety. These disorders may evolve owing to one or more of an array of neuronal changes that occur in several brain regions. It seems likely that these stressor-provoked neurochemical alterations are moderated by genetic determinants, as well as by a constellation of experiential and environmental factors. Indeed, animal studies have shown that vulnerability to depressive-like behaviors involve mechanisms similar to those associated with human depression (e.g., altered serotonin, corticotropin releasing hormone and their receptors, growth factors), and that the effects of stressors are influenced by previous stressor experiences, particularly those encountered early in life. These stressor effects might reflect sensitization of neuronal functioning, phenotypic changes of processes that lead to neurochemical release or receptor sensitivity, or epigenetic processes that modify expression of specific genes associated with stressor reactivity. It is suggested that depression is a life-long disorder, which even after effective treatment, has a high rate of re-occurrence owing to sensitized processes or epigenetic factors that promote persistent alterations of gene expression.
Evaluation of exploration and risk assessment in pre-weaning mice using the novel cage test
2008, Physiology and Behavior
Exploration and risk behaviour (risk assessment/risk taking) are critical to enable mice to cope with novel situations and gain control over their environment. Evaluation of those behaviours would therefore be a useful part of early phenotypic characterization of genetically modified mice, allowing early detection of behavioural phenotypes that require special attention and/or are of scientific interest. This study aimed to evaluate exploration and risk behaviour in pre-weaning mice using the novel cage test, which consists in exploration of a novel, clean, Makrolon type III cage. The results of this test were compared with those obtained in more complex and established tests to which the same mice were subjected as adolescents and young adults.
Mice of two inbred strains (129S6/Bkl, n = 10; C57BL/6Bkl, n = 10) and one hybrid (B6CBAF1/Bkl, n = 10) were used for validation of the test. The animals were tested in the novel cage (at weaning), the open field test (at 5 weeks), and from 9 weeks of age in three other tests: the elevated plus-maze, the concentric square field and the rat exposure test.
The novel cage test effectively detected strain differences in pre-weaning mice as regards exploration and risk behaviour and the results were largely consistent with those obtained in the established tests later in life. In all tests 129S6 displayed a low locomotion and high risk assessment, while C57BL/6 and B6CBAF1 showed high locomotion and exploration. In addition high levels of risk taking were observed in C57BL/6.
The novel cage test is rapid, requires no special equipment and is as discriminatory as more complex tests in detecting strain/genotype differences. This suggests that the novel cage test is a valuable tool for evaluation of exploration, risk assessment and risk taking in juvenile mice.
Corticotropin releasing hormone receptor alterations elicited by acute and chronic unpredictable stressor challenges in stressor-susceptible and resilient strains of mice
2007, Behavioural Brain Research
Stressors increase corticotropin releasing hormone (CRH) functioning in hypothalamic and frontal cortical brain regions, and thus may contribute to the provocation of anxiety and depressive disorder. As the effects of stressors on these behavioral changes are more pronounced in some strains of mice (e.g., BALB/cByJ) than in others (e.g., C57BL/6ByJ), the present investigation assessed whether acute and chronic stressors would differentially influence CRH receptor immunoreactivity (ir-CRHr) and CRH receptor mRNA expression (CRH₁ and CRH₂) in the orbital frontal cortex (OFC) of these strains. An acute noise stressor, and to a greater extent a chronic, variable stressor regimen reduced ir-CRHr in BALB/cByJ mice. In contrast, in the hardier C57BL/6ByJ mice the acute stressor increased ir-CRHr in portions of the OFC, whereas a chronic stressor tended to reduce ir-CRHr. However, whereas the acute stressor did not influence CRH₁ mRNA expression, the chronic stressor increased CRH₁ mRNA expression in both mouse strains. The CRH₂ expression appeared in low abundance in both strains and was unaltered by the stressor. In addition to the OFC variations, quantitative immunohistochemistry indicated that the chronic stressor treatment increased CRH immunoreactivity in the median eminence of C57BL/6ByJ mice, but co-expression of CRH and arginine vasopressin (AVP) immunoreactivity was not provoked by the stressors. The data support the view that stressors provoke marked variations of ir-CRHr in the OFC that might contribute to the differential anxiety/depression-like profiles ordinarily apparent in the stressor-vulnerable and -resilient mouse strains.
Environmental enrichment decreases responding for visual novelty
2006, Behavioural Processes
Previous research has demonstrated that rats reared in an enriched condition (EC) with novel objects and social partners self-administer less amphetamine compared to rats raised in an isolated condition (IC). However, it is unclear if the enrichment-induced decrease in stimulant self-administration generalizes to non-drug rewards such as those provided by novel environmental stimuli. In the current study, EC, IC, and social condition (SC) rats were raised from 21 to 51 days of age before being tested in a two-lever operant conditioning chamber in which responding on one lever (active lever) resulted in illumination of a cue light. In Experiment 1, rats were initially assessed for baseline responding (no contingency) and then the contingent light was introduced. EC rats responded less than IC rats for the contingent light stimulus; however, EC rats also displayed a lower rate of baseline responding. In Experiment 2, rats were trained initially to lever press for a sucrose reward to decrease differences in baseline responding. While sucrose pretraining decreased baseline response differences between groups, EC rats still responded less for the contingent light stimulus than IC or SC rats. These results suggest that environmental enrichment decreases the incentive value of visual novelty.

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²: Present address: Department of Anatomy, UMDNJ-Rutgers Medical School, Piscataway, New Jersey 08854.

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Genetic factors and the measurement of exploratory activity

Animal Behaviour

Brain Research

Physiology and Behavior

Physiology and Behavior

Behavioral Biology

Behaviorial Biology

Behavioral Biology

Recombinant-inbred strains

Recombinant inbred strains and bilineal congenic strains