Intact neurogenesis is required for benefits of exercise on spatial memory but not motor performance or contextual fear conditioning in C57BL/6J mice

Clark, Peter; Brzezinska, Weronika J.; Thomas, Monika; Ryzhenko, N.A.; Toshkov, S; Rhodes, Justin S.

doi:10.1016/j.neuroscience.2008.06.051

Cited by 208 publications

(260 citation statements)

References 62 publications

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“…Unlimited access to voluntary wheel running generally improves memory in C57BL/6J mice [36,37]. The lack of behavioural and cognitive effects of intermittent wheel running in our study raises the question of whether there are optimal levels of exercise for behavioural changes to occur.…”

Section: Intermittent Voluntary Wheel Running Does Not Alter Behavioumentioning

confidence: 58%

“…Although mice are nocturnal and, when given unlimited access to a running wheel, they preferentially exercise during the night, running distances were only found to be affected during the light phase when access to exercise was given for more than 1 hour [39]. However, C57BL/6J mice had to run for at least 3 hours at night to demonstrate a significant increase in hippocampal neurogenesis [39], a mechanism thought to mediate the cognitionenhancing effects of exercise [37,40]. It is therefore possible that the behavioural impact of intermittent exercise would be greater if it was applied during the dark phase of the cycle.…”

Section: Intermittent Voluntary Wheel Running Does Not Alter Behavioumentioning

confidence: 99%

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Corticosterone and dopamine D2/D3 receptors mediate the motivation for voluntary wheel running in C57BL/6J mice

Ebada

Kendall

Pardon

2016

Behavioural Brain Research

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Number of tables: 1Number of words in the abstract: 248Number of words in the manuscript (including tables and figure legends): 6,639Number of words in the introduction: 1,290Number of words in the discussion: 1,243 ABSTRACT Physical exercise can improve cognition but whether this is related to motivation levels is unknown. Voluntary wheel running is a rewarding activity proposed as a model of motivation to exercise. To question the potential effects of exercise motivation on subsequent behaviour, we used a pharmacological approach targeting some reward mechanisms. The stress hormone corticosterone has rewarding effects mediated by activation of low affinity glucocorticoid receptors (GR). To investigate whether corticosterone synthesis motivates exercise via activation of GRs and subsequently, impacts on behaviour, we treated C57BL/6J mice acutely with the inhibitor of corticosterone synthesis metyrapone (35 mg/kg) or repeatedly with the GR antagonist mifepristone (30 mg/kg) prior to 1-hour running wheel sessions. To investigate whether reducing motivation to exercise impacts on behaviour, we antagonised running-induced dopamine D2/D3 receptors activation with sulpiride (25 or 50 mg/kg) and assessed locomotor, anxiety-related and memory performance after 20 running sessions over 4 weeks. We found that corticosterone synthesis contributes to running levels, but the maintenance of running behaviour was not mediated by activation of GRs. Intermittent exercise was not associated with changes in behavioural or cognitive performance. The persistent reduction in exercise levels triggered by sulpiride also had limited impact on behavioural performance, although the level of performance for some behaviours was related to the level of exercise. Altogether, these findings indicate that corticosterone and dopamine D2/D3 receptor activation contribute to the motivation for wheel running, but suggest that motivation for exercise is not a sufficient factor to alter behaviour in healthy mice.

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Section: Intermittent Voluntary Wheel Running Does Not Alter Behavioumentioning

confidence: 58%

Section: Intermittent Voluntary Wheel Running Does Not Alter Behavioumentioning

confidence: 99%

Corticosterone and dopamine D2/D3 receptors mediate the motivation for voluntary wheel running in C57BL/6J mice

Ebada

Kendall

Pardon

2016

Behavioural Brain Research

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“…However, studies in which newly born cells were ablated in runners did not always have consistent results. For example, some researchers found that irradiation of newly born cells in running mice selectively blocked improvement in a general test of hippocampal function, water maze learning (40), but not in contextual fear conditioning (40,41), whereas others reported opposite findings (42). We propose that these discrepant findings might be explained in terms of differences in the requirements for spatial pattern separation.…”

Section: Discussionmentioning

confidence: 76%

Running enhances spatial pattern separation in mice

Creer

Romberg

Saksida

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

456

464

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Increasing evidence suggests that regular exercise improves brain health and promotes synaptic plasticity and hippocampal neurogenesis. Exercise improves learning, but specific mechanisms of information processing influenced by physical activity are unknown. Here, we report that voluntary running enhanced the ability of adult (3 months old) male C57BL/6 mice to discriminate between the locations of two adjacent identical stimuli. Improved spatial pattern separation in adult runners was tightly correlated with increased neurogenesis. In contrast, very aged (22 months old) mice had impaired spatial discrimination and low basal cell genesis that was refractory to running. These findings suggest that the addition of newly born neurons may bolster dentate gyrus-mediated encoding of fine spatial distinctions.

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“…To summarize, a clear disruption of trace eye-blink conditioning has been described (Shors et al 2001(Shors et al , 2002, whereas conflicting results have been reported for contextual fear conditioning. Although some studies reported impairment in generating and/or retrieving contextual fear memory Winocur et al 2006;Farioli-Vecchioli et al 2008;Imayoshi et al 2008;Wojtowicz et al 2008;Deng et al 2009;Hernandez-Rabaza et al 2009), opposite results were found in other studies (Shors et al 2002;Clark et al 2008;Dupret et al 2008;Kitamura et al 2009). …”

Section: Causationmentioning

confidence: 86%

Interaction between Neurogenesis and Hippocampal Memory System: New Vistas

Abrous

Wojtowicz

2015

Cold Spring Harb Perspect Biol

101

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During the last decade, the questions on the functionality of adult neurogenesis have changed their emphasis from if to how the adult-born neurons participate in a variety of memory processes. The emerging answers are complex because we are overwhelmed by a variety of behavioral tasks that apparently require new neurons to be performed optimally. With few exceptions, the hippocampal memory system seems to use the newly generated neurons for multiple roles. Adult neurogenesis has given the dentate gyrus new capabilities not previously thought possible within the scope of traditional synaptic plasticity. Looking at these new developments from the perspective of past discoveries, the science of adult neurogenesis has emerged from its initial phase of being, first, a surprising oddity and, later, exciting possibility, to the present state of being an integral part of mainstream neuroscience. The answers to many remaining questions regarding adult neurogenesis will come along only with our growing understanding of the functionality of the brain as a whole. This, in turn, will require integration of multiple levels of organization from molecules and cells to circuits and systems, ultimately resulting in comprehension of behavioral outcomes.

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Intact neurogenesis is required for benefits of exercise on spatial memory but not motor performance or contextual fear conditioning in C57BL/6J mice

Cited by 208 publications

References 62 publications

Corticosterone and dopamine D2/D3 receptors mediate the motivation for voluntary wheel running in C57BL/6J mice

Corticosterone and dopamine D2/D3 receptors mediate the motivation for voluntary wheel running in C57BL/6J mice

Running enhances spatial pattern separation in mice

Interaction between Neurogenesis and Hippocampal Memory System: New Vistas

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