Early deprivation induces competitive subordinance in C57BL/6 male mice

Abstract

Rodent models have been widely used to investigate the impact of early life stress on adult health and behavior. However, the social dimension has rarely been incorporated into the analysis due to methodological limitations. This study characterized the effects of neonatal social isolation (early deprivation, ED) on adult C57BL/6 mouse behavior in a social context using our recently developed behavioral test protocols for group-housed mice. During the first two postnatal weeks, half of the pups per dam were separated from their dam and littermates for 3h per day (ED group). Post weaning, ED and control pups were electronically tagged and co-housed. At 12weeks, the mixed cohorts were transferred to IntelliCages, equipped with computer-controlled operant chambers. Access to the chambers was used as an index to analyze novel object response, behavioral flexibility, and competitive dominance with minimal experimenter intervention. In general, ED had greater effects on males; ED males exhibited reduced body weight, increased novelty response, and were subordinate to control littermates when competing for reward access. Male ED mice also demonstrated mildly impaired reversal learning. Analyzing gene expression changes in brain regions controlling emotion, stress, spatial memory, and executive function revealed reduced BDNF and c-Fos in hippocampal CA1, enhanced c-Fos in the basolateral amygdala, reduced Map2 while enhanced HSD11β2 in prefrontal cortex of ED males. In male mice, it was suggested that neonatal social isolation results in sustained changes in social behavior with altered function of limbic and frontal cortices.

Gene expression patterns and environmental enrichment-induced effects in the hippocampi of mice suggest importance of Lsamp in plasticity

“…We did not detect any statistically relevant enrichment-induced differences of Lsamp expression in the frontal cortex, hypothalamus, thalamus, ventral striatum, or temporal lobe. It has been shown that social isolation affects the expression level of several genes (Benner et al, 2014; Siuda et al, 2014) and Lsamp -deficient mice tend to be insensitive to separation from the group (Innos et al, 2012); isolation stress had no effect on the expression levels of Lsamp transcripts in any of the brain areas investigated in the current study.…”

Maternal Deprivation Influences Pup Ultrasonic Vocalizations of C57BL/6J Mice

“…For instance, adult rats that experienced repeated MD in early life showed enhanced vulnerability to stress, as demonstrated by an increase in depressive behaviors, such as a lower sucrose preference in a sucrose preference test and a longer immobility time in a forced swimming test [13]. Benner suggested that early deprivation can induce competitive subordinance and impaired reversal learning with altered functions of the limbic and frontal cortices in adult C57BL/6 mice [14]. However, the effect of MD in early life, particularly the neonatal days during which multiple neural systems are established [15,16], has rarely been investigated, which may be partially due to the lack of parameters that can be quantitatively analyzed in very young rodents.…”

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“…Our study demonstrated that isolated rearing mice induced spatial and non-spatial cognitive deficits as well as abnormal work memory, which are consistent with previous published papers ( Khodaie et al, 2015). Social isolation results in cognitive dysfunction, which is also supported by the view that individual rearing has effects on impairing cognition ability on the following behavior tests (Benner et al, 2014;Green & McCormick, 2013). In the rotating T-maze, 6 weeks isolation leads to reversal-learning impairment in Wistar rats (Quan et al, 2010); C57BL/6J and DBA/2 strains reared in 7 weeks isolation since postnatal day 28 show significantly impaired fear conditioning (Võikar et al, 2005); The learning memory ability decreases in isolation-reared rats by the performance of Morris water maze and attention set shifting.…”