The mammalian brain is highly plastic. Environmental enrichment（EE） has been widely used as a noninvasive means to enhance brain plasticity. EE extensively improves brain functions，including development，aging，recovery from damages and response to stress stimulations，thereby benefits the treatment of neurodevelopmental disorders，neurodegenerative diseases，stroke and traumatic brain injury，affective disorders and substance addiction. However，EE has largely remained a laboratory phenomenon with little translation to the clinical setting. A critical strategy for the clinical translation of EE is to identify key molecular substrate of effects of EE on brain plasticity.