Rats treated with low dose irradiation, to inhibit adult hippocampal neurogenesis, and control rats were administered a non-matching-to-sample (NMTS) task, which measured conditional rule learning and memory for specific events, and a test of fear conditioning in which a discrete CS was paired with an aversive US in a complex environment. Irradiated rats were impaired on the NMTS task when the intervals between sample and test trials were relatively long, and in associating the shock-induced fear with contextual cues in the fear conditioning task. Irradiated rats were not impaired in learning the basic NMTS rule or in performing that task when the intervals between the sample and test trials were short. Nor were there group differences in conditioning the fear response to the CS in the fear conditioning task. The results, which extend the range of hippocampus-dependent tasks that can be said to be vulnerable to the effects of neurogenesis suppression, support the hypothesis that new hippocampal cells generated in adulthood participate in a broad range of hippocampal functions.
Neuronal activity-induced gene expression modulates the function and plasticity of the nervous system. It is unknown whether and to what extent neuronal activity may trigger changes in chromatin accessibility, a major mode of epigenetic regulation of gene expression. Here we compared chromatin accessibility landscapes of adult mouse dentate granule neurons in vivo before and after synchronous neuronal activation using ATAC-seq. We found widespread, genome-wide changes one hour after activation, with enrichment of gained-open sites at active enhancer regions and at binding sites for AP1 complex components, including cFos. Some changes remain stable for at least twenty-four hours. Functional analysis further implicates a critical role of cFos in initiating, but not maintaining, neuronal activity-induced chromatin opening. Our results reveal dynamic changes of chromatin accessibility in the adult mammalian brain and suggest an epigenetic mechanism by which transient neuronal activation leads to dynamic changes in gene expression via modifying chromatin accessibility.
Probiotics, defined as live bacteria or bacterial products, confer a significant health benefit to the host, including amelioration of anxiety-like behavior and psychiatric illnesses. Here we administered Lactobacillus plantarum PS128 (PS128) to a germ-free (GF) mouse model to investigate the impact of the gut-brain axis on emotional behaviors. First, we demonstrated that chronic administration of live PS128 showed no adverse effects on physical health. Then, we found that administration of live PS128 significantly increased the total distance traveled in the open field test and decreased the time spent in the closed arm in the elevated plus maze test, whereas the administration of PS128 had no significant effects in the depression-like behaviors of GF mice. Also, chronic live PS128 ingestion significantly increased the levels of both serotonin and dopamine in the striatum, but not in the prefrontal cortex or hippocampus. These results suggest that the chronic administration of PS128 is safe and could induce changes in emotional behaviors. The behavioral changes are correlated with the increase in the monoamine neurotransmitters in the striatum. These findings suggest that daily intake of the L. plantarum strain PS128 could improve anxiety-like behaviors and may be helpful in ameliorating neuropsychiatric disorders.
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