Mouse genetic differences in voluntary wheel running, adult hippocampal neurogenesis and learning on the multi-strain-adapted plus water maze

Merritt, Jennifer R.; Rhodes, Justin S.

doi:10.1016/j.bbr.2014.11.030

Cited by 43 publications

(25 citation statements)

References 44 publications

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“…This difference was not due to gross learning or motoric effects in S1, because the strain responded at a higher rate for at least one reward type (food). Moreover, previous studies show that S1 mice exhibit good learning across a range of operant- and maze-based behavioral assays (Clapcote & Roder, 2004; Holmes et al, 2002; Merritt & Rhodes, 2015). Thus, the lesser responding for ethanol-containing solutions in S1 mice likely reflects the aversion to ethanol, whether straight or sweetened, that has been reported in this strain previously (Rhodes et al, 2007; Yoneyama et al, 2008).…”

Section: Discussionmentioning

confidence: 94%

Mouse strain differences in punished ethanol self-administration

Halladay

Kocharian

Holmes

2017

Alcohol

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Determining the neural factors contributing to compulsive behaviors such as alcohol-use disorders (AUDs) has become a significant focus of current preclinical research. Comparison of phenotypic differences across genetically distinct mouse strains provides one approach to identify molecular and genetic factors contributing to compulsive-like behaviors. Here we examine a rodent assay for punished ethanol self-administration in four widely used inbred strains known to differ on ethanol-related behaviors: C57BL/6J (B6), DBA/2J (D2), 129S1/SvImJ (S1), and BALB/cJ (BALB). Mice were trained in an operant task (FR1) to reliably lever-press for 10% ethanol using a sucrose-fading procedure. Once trained, mice received a punishment session in which lever pressing resulted in alternating ethanol reward and footshock, followed by tests to probe the effects of punishment on ethanol self-administration. Results indicated significant strain differences in training performance and punished attenuation of ethanol self-administration. S1 and BALB showed robust attenuation of ethanol self-administration after punishment, whereas behavior in B6 was attenuated only when the punishment and probe tests were conducted in the same contexts. By contrast, D2 were insensitive to punishment regardless of context, despite receiving more shocks during punishment and exhibiting normal footshock reactivity. Additionally, B6, but not D2, reduced operant self-administration when ethanol was devalued with a bitter tastant. B6 and D2 showed devaluation of sucrose self-administration, and punished suppression of sucrose seeking was context dependent in both the strains. While previous studies have demonstrated avoidance of ethanol in D2, particularly when ethanol is orally available from a bottle, current findings suggest this strain may exhibit heightened compulsive-like self-administration of ethanol, although there are credible alternative explanations of the phenotype of this strain. In sum, these findings offer a foundation for future studies examining the neural and genetic factors underlying AUDs.

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Section: Discussionmentioning

confidence: 94%

Mouse strain differences in punished ethanol self-administration

Halladay

Kocharian

Holmes

2017

Alcohol

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“…Several studies have demonstrated that increasing production of adult born neurons in the hippocampus; that is increasing adult neurogenesis levels improves performance in context discrimination while decreasing neurogenesis has the opposite effect (Clemenson et al, 2015; D. J. Creer, C. Romberg, L. M. Saksida, H. van Praag, & T. J. Bussey, 2010; Danielson et al, 2016; Frankland et al, 1998; Merritt & Rhodes, 2015; Sahay et al, 2011). Young neurons are more sensitive to perforant pathway input necessary for driving the encoding of new contexts (Frankland et al, 2013; Lacar et al, 2014; Wojtowicz, 2012).…”

Section: 0 Discussionmentioning

confidence: 99%

Aged dominant negative p38α MAPK mice are resistant to age-dependent decline in adult-neurogenesis and context discrimination fear conditioning

Cortez

Bulavin

et al. 2017

Behavioural Brain Research

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A major aspect of mammalian aging is the decline in functional competence of many self-renewing cell types, including adult-born neuronal precursors. Since age-related senescence of self-renewal occurs simultaneously with chronic up-regulation of the p38MAPKalpha (p38α) signaling pathway, we used the dominant negative mouse model for attenuated p38α activity (DN-p38αAF/+ ) in which Thr180 and Tyr182 are mutated (T→A/Y→F) to prevent phosphorylation activation (DN-p38αAF/+) and kinase activity. As a result, aged DN-p38αAF/+ mice are resistant to age-dependent decline in proliferation and regeneration of several peripheral tissue progenitors when compared to wild-type littermates. Aging is the major risk factor for non-inherited forms of Alzheimer’s disease (AD); environmental and genetic risk factors that accelerate the senescence phenotype are thought to contribute to an individual’s relative risk. In the present study, we evaluated aged DN-p38αAF/+ and wildtype littermates in a series of behavioral paradigms to test if p38α mutant mice exhibit altered baseline abnormalities in neurological reflexes, locomotion, anxiety-like behavior, and age-dependent cognitive decline. While aged DN-p38αAF/+ and wildtype littermates appear equal in all tested baseline neurological and behavioral parameters, DN-p38αAF/+ exhibit superior context discrimination fear conditioning. Context discrimination is a cognitive task that is supported by proliferation and differentiation of adult-born neurons in the dentate gyrus of the hippocampus. Consistent with enhanced context discrimination in aged DN-p38αAF/+, we discovered enhanced production of adult-born neurons in the dentate gyrus of DN-p38αAF/+ mice compared to wildtype littermates. Our findings support the notion that p38α inhibition has therapeutic utility in aging diseases that affect cognition, such as AD.

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“…Alternatively, the mouse strain used in the current study (generated on a BL6129 background) may have been a confounding factor by potentially limiting our ability to detect any downregulation of new neurons. In several independent studies examining the role of genetic influence on the baseline level of hippocampal neurogenesis, the B6129SF1 and 129Sv were among the strains showing the lowest levels of newborn neurons (Clark et al, ; Kempermann, Kuhn, & Gage, ; Merritt & Rhodes, ).…”

Section: Introductionmentioning

confidence: 99%

Deletion of TLX and social isolation impairs exercise‐induced neurogenesis in the adolescent hippocampus

et al. 2017

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Adolescence is a sensitive period of neurodevelopment during which life experiences can have profound effects on the brain. Hippocampal neurogenesis, the neurodevelopmental process of generating functional new neurons from neural stem cells, occurs throughout the lifespan and has been shown to play a role in learning, memory and in mood regulation. In adulthood it is influenced by extrinsic environmental factors such as exercise and stress. Intrinsic factors that regulate hippocampal neurogenesis include the orphan nuclear receptor TLX (Nr2e1) which is primarily expressed in the neurogenic niches of the brain. While mechanisms regulating adult hippocampal neurogenesis have been widely studied, less is known on how hippocampal neurogenesis is affected during adolescence. The aim of this study was to investigate the influence of both TLX and isolation stress on exercise-induced increases in neurogenesis in running and sedentary conditions during adolescence. Single-(isolation stress) wild type and Nr2e1 -/-mice or pair-housed wild type mice were housed in sedentary conditions or allowed free access to running wheels for 3 weeks during adolescence. A reduction of neuronal survival was evident in mice lacking TLX, and exercise did not increase hippocampal neurogenesis in these Nr2e1 -/-mice. This suggests that TLX is necessary for the pro-neurogenic effects of exercise during adolescence. Interestingly, although social isolation during adolescence did not affect hippocampal neurogenesis, it prevented an exercise-induced increase in neurogenesis in the ventral hippocampus. Together these data demonstrate the importance of intrinsic and extrinsic factors in promoting an exercise-induced increase in neurogenesis at this key point in life. K E Y W O R D Sadolescence, adult neurogenesis, exercise, stress, TLX

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Mouse genetic differences in voluntary wheel running, adult hippocampal neurogenesis and learning on the multi-strain-adapted plus water maze

Cited by 43 publications

References 44 publications

Mouse strain differences in punished ethanol self-administration

Mouse strain differences in punished ethanol self-administration

Aged dominant negative p38α MAPK mice are resistant to age-dependent decline in adult-neurogenesis and context discrimination fear conditioning

Deletion of TLX and social isolation impairs exercise‐induced neurogenesis in the adolescent hippocampus

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