Abstract
In addition to the regulation of social and emotional behaviors, the hypothalamic neuropeptide oxytocin has been shown to stimulate neurogenesis in adult dentate gyrus; however, the mechanisms underlying the action of oxytocin are still unclear. Taking advantage of the conditional knockout mouse model, we show here that endogenous oxytocin signaling functions in a non-cell autonomous manner to regulate survival and maturation of newly generated dentate granule cells in adult mouse hippocampus via oxytocin receptors expressed in CA3 pyramidal neurons. Through bidirectional chemogenetic manipulations, we also uncover a significant role for CA3 pyramidal neuron activity in regulating adult neurogenesis in the dentate gyrus. Retrograde neuronal tracing combined with immunocytochemistry revealed that the oxytocin neurons in the paraventricular nucleus project directly to the CA3 region of the hippocampus. Our findings reveal a critical role for oxytocin signaling in adult neurogenesis.
Highlights
In addition to the regulation of social and emotional behaviors, the hypothalamic neuropeptide oxytocin has been shown to stimulate neurogenesis in adult dentate gyrus; the mechanisms underlying the action of oxytocin are still unclear
In the CA3, 3.8 ± 0.7% of Venuspositive cells expressed GAD67 immunoreactivity (Supplementary Fig. 1a, b). These results indicate that OXT receptor (OXTR) is not expressed in the neural progenitor cells that reside within the subgranular zone or mature granule cells of adult dentate gyrus (DG) and a small subset of hilar GABAergic neurons express OXTR
OXTR is not expressed in neural progenitor cells reside within the subgranular zone or mature granule cells of adult DG, whereas it is enriched in the CA2 and CA3 of the hippocampus
Summary
In addition to the regulation of social and emotional behaviors, the hypothalamic neuropeptide oxytocin has been shown to stimulate neurogenesis in adult dentate gyrus; the mechanisms underlying the action of oxytocin are still unclear. Taking advantage of the conditional knockout mouse model, we show here that endogenous oxytocin signaling functions in a non-cell autonomous manner to regulate survival and maturation of newly generated dentate granule cells in adult mouse hippocampus via oxytocin receptors expressed in CA3 pyramidal neurons. Despite these study points toward a crucial role for OXT in facilitating hippocampal plasticity and function, exogenous application of OXT has been reported to exert a neurotrophic effect to increase adult neurogenesis even when experienced to stressful situations[17]. Does endogenous OXT signaling regulates adult neurogenesis through a cell autonomous or non-cell autonomous mechanism? Using a Cre/loxP recombinase-based strategy to delete Oxtr, we report here that endogenous OXT signaling controls adult hippocampal neurogenesis through an indirect non-cell autonomous mechanism by OXTR expressed in CA3 pyramidal neurons Is OXTR expressed in adult hippocampal neural progenitor cells? Second, does endogenous OXT signaling regulates specific stages of adult hippocampal neurogenesis? does endogenous OXT signaling regulates adult neurogenesis through a cell autonomous or non-cell autonomous mechanism? Using a Cre/loxP recombinase-based strategy to delete Oxtr, we report here that endogenous OXT signaling controls adult hippocampal neurogenesis through an indirect non-cell autonomous mechanism by OXTR expressed in CA3 pyramidal neurons
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