SOCIAL DEPRIVATION AND VOLUNTARY RUNNING BIDIRECTIONALLY AFFECT ADULT HIPPOCAMPAL NEUROGENESIS VIA CTBP1

In the process of adult neurogenesis, new neurons are generated from multipotent precursor cells, named neural precursor cells (NPCs). Adult hippocampal neurogenesis is indispensable for cognitive and emotional brain function. CtBP1 is relevant for human neurodevelopment as well, de novo CtBP1 mutations cause a rare neurodevelopmental disease called HADDTS (Hypotonia, Ataxia, Developmental Delay, and Tooth-Enamel Defects Syndrome). We studied the effect of CtBP1 in the context of adult neurogenesis in vivo on mice and found that CtBP1 loss lowers the number of newly generated mature hippocampal neurons. In this study we aimed to investigate how housing conditions affect neurogenesis in adult mice and whether CtBP1 plays a role in the environment-driven regulation of adult neurogenesis. Therefore, we analyzed adult neurogenesis in socially and single-housed control and heterozygote CtBP1 animals, with and without access to a running wheel. Neurogenesis was similar in single-housed animals across genotypes. Social housing robustly elevated hippocampal neurogenesis in control animals, but had little effect on neurogenesis in CtBP1 heterozygote mice. Meanwhile, voluntary running differentially affected proliferation, lineage progression, and maturation of newly generated cells between genotypes and had sex-specific effects in CtBP1 heterozygotes. The differences in proliferation of NPCs in in vitro and in vivo conditions were studied using EdU labeling. These results indicate that CtBP1 is important for accurate regulation of adult hippocampal neurogenesis by external stimuli and indicate that CtBP1 affects the proliferation potential of NPCs and their differentiation, which ultimately influences adult neurogenesis.