The Social Component of Environmental Enrichment Is a Pro-neurogenic Stimulus in Adult c57BL6 Female Mice

Abstract

In rodents, the hippocampal dentate gyrus gives rise to newly generated dentate granule cells (DGCs) throughout life. This process, named adult hippocampal neurogenesis (AHN), converges in the functional integration of mature DGCs into the trisynaptic hippocampal circuit. Environmental enrichment (EE) is one of the most potent positive regulators of AHN. This paradigm includes the combination of three major stimulatory components, namely increased physical activity, constant cognitive stimulation, and higher social interaction. In this regard, the pro-neurogenic effects of physical activity and cognitive stimulation have been widely addressed in adult rodents. However, the pro-neurogenic potential of the social aspect of EE has been less explored to date. Here we tackled this question by specifically focusing on the effects of a prolonged period of social enrichment (SE) in adult female C57BL6 mice. To this end, 7-week-old mice were housed in groups of 12 per cage for 8 weeks. These mice were compared with others housed under control housing (2–3 mice per cage) or EE (12 mice per cage plus running wheels and toys) conditions during the same period. We analyzed the number and morphology of Doublecortin-expressing (DCX + ) cells. Moreover, using RGB retroviruses that allowed the labeling of three populations of newborn DGCs of different ages in the same mouse, we performed morphometric, immunohistochemical, and behavioral determinations. Both SE and EE increased the number and maturation of DCX + cells, and caused an increase in dendritic maturation in certain populations of newborn DGCs. Moreover, both manipulations increased exploratory behavior in the Social Interaction test. Unexpectedly, our data revealed the potent neurogenesis-stimulating potential of SE in the absence of any further cognitive stimulation or increase in physical activity. Given that an increase in physical activity is strongly discouraged under certain circumstances, our findings may be relevant in the context of enhancing AHN via physical activity-independent mechanisms.

Experience-Dependent Structural Plasticity of Adult-Born Neurons in the Aging Hippocampus

“…Enriched environment enhances HC-mediated learning and plasticity (van Praag et al, 2000; Moreno-Jiménez et al, 2005; Baroncelli et al, 2010; Bergami et al, 2015; Alvarez et al, 2016; Moreno-Jimenez et al, 2019). A brief exposure of young-adult mice to EE was shown to promote new GC integration at an early developmental stage (second week), an effect mediated by the depolarizing action of GABAergic interneurons (Chancey et al, 2013; Alvarez et al, 2016).…”

Environmental enrichment delays the development of stereotypic behavior and reduces variability in behavioral experiments using California mice (Peromyscus californicus)

“…The fact that both large and large+EE had similar effects on exploratory behaviors suggests that increased space and social complexity, in the absence of environmental enrichment, are sufficient to trigger an effect on motivated responses. Studies in female C57 mice showed similar results: just the social component of enriched environments could explain an increase in both non-social and social exploration time, which was correlated with an increased number of doublecortin expressing cells in the hippocampus, indicating increased neurogenesis (Moreno-Jiménez et al, 2019).…”

Environmental enrichment reverses memory impairment in B3-ARKO mice

“…The efficacy of the EE protocol in reversing the short-and long-term memory deficit in young mice due to the lack of Adrβ3 could be explained by the findings of several previous studies showing that cognitive enrichment in rats contributes to better learning and the performance of declarative and procedural memory tasks. The increase in the dendritic tree in the third layer of the pyramidal neurons of the temporal lobe, changes in synaptic organization and an increase in the amount of intersections in both the basal and apical dendrites suggests a change in plasticity that involves neural reorganization and an increase in the number of neuronal contacts and the formation of a more complex neuronal network (33)(34)(35).…”