Whole-brain Activations And Plasiticity Associated With Environmental Enrichment:An MRI Study

An enriched environment(EE)offers multiple dimensions of stimulus to the brain,including physical activities,multisensory/cognitive loading and social interactions.The effects of EE exposure on brain plasticity have been studied extensively in animal models at behavioral,anatomical,physiological,biochemical and molecular levels.It was shown that EE exposure can induce functional and structural neuroplasticity,and different duration of EE exposure was associated with different changes in cognitive processes,neural activity and plasticity.The potential of using EE as a treatment/rehabilitation measure for neurological/psychiatric disorders has also been explored.But most of these studies have used a long-term EE exposure and focused on one or at most a few regions of interest within the brain,such as the hippocampus,prefrontal cortex,sensory/motor cortices and striatum.With the rapid development of magnetic resonance imaging recently,it is possible to investigate the brain function and structure at the whole brain level unbiasedly.However,in vivo neuroimaging studies on brain function and structure during EE exposure are scarce in the literature.An unbiased mapping of whole-brain activities and structural changes associated with EE exposure could shed light on the neurobiological mechanisms underlying EE-related neuroplasticity.In this work,the effects of EE exposure on brain function and structure at two different duration(7-day and 2-day)were studied in normal adult mice with manganese-enhanced magnetic resonance imaging(MEMRI),and assisted with immunohistochemical assessments.To better distinguish the 2-day EE exposure from the 7-day sub-acute EE exposure,it was defined as an acute exposure in this dissertation.The main contents are as follows:Firstly,in vivo MEMRI was used to map the accumulative whole-brain activities in freely-moving mice during a 7-day sub-acute EE exposure,followed by c-Fos immunochemical assessments.Relative to the mice residing in a standard environment(SE),the mice subjected to EE treatment had significantly enhanced regional MEMRI signal intensities in the prefrontal cortex,somatosensory cortices,basal ganglia,amygdala,motor thalamus,lateral hypothalamus,ventral hippocampus and midbrain dopaminergic areas at the end of the 7-day exposure.Some of,but not all,the brain regions in the EE-treated mice showing enhanced MEMRI signal intensity had accompanying increases in c-Fos expression.The EE-treated mice were also found to have significantly increased overall amount of food consumption,decreased body weight gain and upregulated tyrosine hydroxylase(TH)expression in the midbrain dopaminergic areas.Secondly,in vivo MEMRI was further used to map the changes of whole-brain structure associated with the 7-day EE exposure in freely-moving mice.It was found that MEMRI could detect changes in the brain volume of adult mice after a 7-day sub-acute EE exposure.Combined with the results of brain activities above,it was found that some of,but not all,the brain regions in the EE-treated mice showing enhanced MEMRI signal intensity had accompanying increases in brain volume.But there are strong structural connections between the brain regions of increased volume and the brain regions of enhanced MEMRI signal intensity.The EE-induced increase in the volume of dentate gyrus(DG)was accompanied by an increase in cell proliferation,but the new neurons were not recruited into the functional network as reveled by the Brd U staining and Brd U/c-Fos double staining.This also indicates that the observed increase in the number of c-Fos positive cells in DG is not due to cell proliferation.Finally,in vivo MEMRI was used to map the accumulative whole-brain activities and the changes of brain volume associated with a 2-day acute EE exposure in freely-moving mice.It was shown that the changes of brain activities and brain volume after a 2-day acute EE exposure can be detected with MEMRI.Combined with the results of the 7-day sub-acute EE exposure,it was indicated that changes in the function and structure of some brain regions had begun in the early stage of EE exposure and continued to operate for a week.Dynamic changes in functional activity and structural plasticity of the brain were also observed during the two EE exposure of different duration.Taken together,the work in this dissertation demonstrated that EE exposure was associated with functional and structural changes involving distributed brain regions in multiple networks.And different duration of EE exposure was accompanied by different functional and structural changes.These findings might have served as the substrate of EErelated neuroplasticity and the beneficial effects of EE treatment on neurological/psychiatric conditions including drug addiction,Parkinson's disease and eating disorder,providing new strategy to treat these disorders.