Browsing by Author "Epp, Jonathan R."

Now showing 1 - 4 of 4
  • Thumbnail Image
    ItemOpen Access
    Adult neurogenesis mediates forgetting of multiple types of memory in the rat
    (2021-06-26) Scott, Gavin A.; Terstege, Dylan J.; Roebuck, Andrew J.; Gorzo, Kelsea A.; Vu, Alex P.; Howland, John G.; Epp, Jonathan R.
    Abstract The formation and retention of hippocampus-dependent memories is impacted by neurogenesis, a process that involves the production of new neurons in the dentate gyrus of the hippocampus. Recent studies demonstrate that increasing neurogenesis after memory formation induces forgetting of previously acquired memories. Neurogenesis-induced forgetting was originally demonstrated in mice, but a recent report suggests that the same effect may be absent in rats. Although a general species difference is possible, other potential explanations for these incongruent findings are that memories which are more strongly reinforced become resilient to forgetting or that perhaps only certain types of memories are affected. Here, we investigated whether neurogenesis-induced forgetting occurs in rats using several hippocampus-dependent tasks including contextual fear conditioning (CFC), the Morris Water Task (MWT), and touchscreen paired associates learning (PAL). Neurogenesis was increased following training using voluntary exercise for 4 weeks before recall of the previous memory was assessed. We show that voluntary running causes forgetting of context fear memories in a neurogenesis-dependent manner, and that neurogenesis-induced forgetting is present in rats across behavioral tasks despite differences in complexity or reliance on spatial, context, or object memories. In addition, we asked whether stronger memories are less susceptible to forgetting by varying the strength of training. Even with a very strong training protocol in the CFC task, we still observed enhanced forgetting related to increased neurogenesis. These results suggest that forgetting due to neurogenesis is a conserved mechanism that aids in the clearance of memories.
  • Thumbnail Image
    ItemOpen Access
    New neurons in old brains: implications of age in the analysis of neurogenesis in post-mortem tissue
    (2022-05-02) Terstege, Dylan J.; Addo-Osafo, Kwaku; Campbell Teskey, G.; Epp, Jonathan R.
    Abstract Adult neurogenesis, the proliferation and integration of newly generated neurons, has been observed in the adult mammalian hippocampus of many species. Numerous studies have also found adult neurogenesis in the human hippocampus, but several recent high-profile studies have suggested that this process is considerably reduced in humans, occurring in children but not in adults. In comparison, rodent studies also show age-related decline but a greater degree of proliferation of new neurons in adult animals. These differences may represent biological species differences or could alternatively be explained by methodological differences in tissue handling and fixation. Here, we examine whether differences in the post-mortem interval between death and tissue fixation might impact subsequent detection of adult neurogenesis due to increased tissue degradation. Because there are fewer new neurons present in older subjects to begin with we hypothesized that, subject age might interact significantly with post-mortem interval in the detection of adult neurogenesis. We analyzed neurogenesis in the hippocampus of rats that were either perfusion-fixed or the brains extracted and immersion-fixed at various post-mortem intervals. We observed an interaction between animal age and the time delay between death and tissue fixation. While similar levels of neurogenesis were observed in young rats regardless of fixation, older rats had significantly fewer labeled neurons when fixation was not immediate. Furthermore, the morphological detail of the labeled neurons was significantly reduced in the delayed fixation conditions at all ages. This study highlights critical concerns that must be considered when using post-mortem tissue to quantify adult neurogenesis.
  • Thumbnail Image
    ItemOpen Access
    The Role of Vesicular Zinc in Modulating Cell Proliferation and Survival in the Developing Hippocampus
    (2022-09) Fu, Selena; Dyck, Richard H.; Antle, Michael C.; Spanswick, Simon C.; Epp, Jonathan R.
    In the brain, vesicular zinc, which refers to a subset of zinc that is sequestered into synaptic vesicles by zinc transporter 3 (ZnT3), has extensive effects in neuronal signaling and modulation. Vesicular zinc-focused research has mainly been directed to its role in the hippocampus, particularly in adult neurogenesis. However, whether vesicular zinc is involved in modulating neurogenesis during the early postnatal period has been less studied. To assess whether vesicular zinc plays a role in early developmental hippocampal neurogenesis, we used ZnT3 knockout (KO) mice, which lack ZnT3 and thus vesicular zinc, to evaluate cell proliferation at three different developmental age points, and the survival of these cells into adulthood. Our primary finding was that male ZnT3 KO mice exhibited lower rates of cell proliferation at P14, but higher numbers of these cells were retained to P60. Additionally, male and female ZnT3 KO mice retained a greater number of cells labelled on P6. These findings suggest that loss of vesicular zinc affects normal cell proliferation and cell survival at different age points during postnatal development. Additionally, we found sex-dependent differences whereby male mice showed higher levels of cell proliferation at P28, as well as higher levels of cell retention for P14-labelled cells, compared to female mice. There were also significant effects of age on cell proliferation and survival. Collectively, our findings offer novel insights into a unique role for vesicular zinc in the modulation of neurogenesis and cell survival during early postnatal development and highlight prominent sex- and age-dependent differences.
  • Thumbnail Image
    ItemOpen Access
    Running-induced neurogenesis reduces CA1 perineuronal net density without substantial temporal delay
    (2024-09-02) Terstege, Dylan J.; Goonetilleke, Duneesha; Barha, Cindy K.; Epp, Jonathan R.
    Abstract Aerobic exercise has many effects on brain function, particularly at the hippocampus. Exercise has been shown to increase the rate of adult neurogenesis within the dentate gyrus and decrease the density of perineuronal nets in area CA1. The relationship between the rate of neurogenesis and the density of perineuronal nets in CA1 is robust; however, these studies only ever examined these effects across longer time scales, with running manipulations of 4 weeks or longer. With such long periods of manipulation, the precise temporal nature of the relationship between running-induced neurogenesis and reduced perineuronal net density in CA1 is unknown. Here, we provided male and female mice with home cage access to running wheels for 0, 1, 2, or 4 weeks and quantified hippocampal neurogenesis and CA1 perineuronal net density. In doing so, we observed a 2-week delay period prior to the increase in neurogenesis, which coincided with the same delay prior to decreased CA1 perineuronal net density. These results highlight the closely linked temporal relationship between running-induced neurogenesis and decreased perineuronal net expression in CA1.