MSK1 is required for the beneficial synaptic and cognitive effects of enriched experience across the lifespan

Positive experiences, such as social interaction, cognitive training and physical exercise, have been shown to ameliorate some of the harms to cognition associated with ageing. Animal models of positive interventions, commonly known as environmental enrichment, strongly influence neuronal morphology and synaptic function and enhance cognitive performance. While the profound structural and functional benefits of enrichment have been appreciated for decades, little is known as to how the environment influences neurons to respond and adapt to these positive sensory experiences. We show that adult and aged male wild-type mice that underwent a 10-week environmental enrichment protocol demonstrated improved performance in a variety of behavioural tasks, including those testing spatial working and spatial reference memory, and an enhancement in hippocampal LTP. Aged animals in particular benefitted from enrichment, performing spatial memory tasks at levels similar to healthy adult mice. Many of these benefits, including in gene expression, were absent in mice with a mutation in an enzyme, MSK1, which is activated by BDNF, a growth factor implicated in rodent and human cognition. We conclude that enrichment is beneficial across the lifespan and that MSK1 is required for the full extent of these experience-induced improvements of cognitive abilities, synaptic plasticity and gene expression. to examine the influence of experience and MSK1 on hippocampal gene expression in aged mice housed in standard or enriched conditions正向体验（如社交互动、认知训练与体育锻炼）已被证实可减轻衰老相关的部分认知损伤。被普遍称为环境丰富化（environmental enrichment）的正向干预动物模型，可显著调控神经元形态与突触功能，并提升认知表现。尽管环境丰富化所带来的显著结构与功能益处已被学界认知数十年，但对于环境如何促使神经元响应并适应这类正向感官体验的机制，目前仍所知甚少。本研究显示，接受10周环境丰富化方案的成年与老年雄性野生型小鼠，在多项行为学任务（包括测试空间工作记忆与空间参考记忆的任务）中表现均得到改善，且海马体长时程增强（LTP）水平显著提升。其中老年小鼠从环境丰富化中获益尤为显著，其空间记忆任务表现可媲美健康成年小鼠。在携带受脑源性神经营养因子（BDNF，一种与啮齿类及人类认知功能相关的生长因子）激活的酶MSK1发生突变的小鼠中，上述多数益处（包括基因表达层面的改变）均未显现。综上，环境丰富化在整个生命周期中均具有积极益处，且MSK1是体验诱导的认知能力、突触可塑性与基因表达改善得以完全实现的必需因子。本研究旨在探究体验与MSK1对饲养于标准环境或丰富环境中的老年小鼠海马体基因表达的影响。