Abstract
Neurogenesis occurs in the adult hippocampus of various animal species. A substantial fraction of newly generated neurons die before they mature, and the survival rate of new neurons are regulated in an experience-dependent manner. Previous study showed that high-frequency stimulation (HFS) of perforant path fibers to the hippocampal dentate gyrus (DG) induces the long-term potentiation (LTP) in the DG, and enhances the survival of newly generated neurons in the DG. In this study, we addressed whether a time period exists during which the survival of new neurons is maximally sensitive to the HFS. We found that the enhancement of cell survival by HFS was exclusively restricted to the specific narrow period during immature stages of new neurons (7-10 days after birth). Furthermore, the pharmacological blockade of LTP induction suppressed the enhancement of cell survival by the HFS. These results suggest that the LTP induction within a narrow critical period of immature stages enhances the survival of newly generated neurons in rat DG.
Highlights
Large numbers of new neurons are generated throughout adulthood in the hippocampal dentate gyrus (DG) of many mammals, including rats, monkeys, and humans [1,2,3]
To clarify the dentate area that is affected by high-frequency stimulation (HFS), we examined the expression of vesl-1S/ Homer-1a mRNA. vesl-1S/Homer-1a is a neural activityregulated gene [21,24,25] whose expression is positively regulated by long-term potentiation (LTP) induction
Previous report shows that the stimulation protocol (288 pulse, 400 Hz), which is intermediate between the HFS (500) and HFS (90), enhances the cell proliferation in the DG [19]
Summary
Large numbers of new neurons are generated throughout adulthood in the hippocampal dentate gyrus (DG) of many mammals, including rats, monkeys, and humans [1,2,3]. The survival rate of new neurons is regulated in an experiencedependent manner, such as environmental enrichment, running wheel exercises, and learning contributing to survival [15,16,17,18]. Previous study shows that high-frequency stimulation (HFS) of perforant path fibers to the DG induces long-term potentiation (LTP) in the DG and enhances the survival of newly-born neurons in the DG [19]. We addressed whether a time period exists during which the survival of new neurons is maximally sensitive to HFS.
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