Abstract
Ablation of adult neurogenesis in mice has revealed that young adult-born granule cells (abGCs) are required for some of the behavioral responses to antidepressants (ADs), yet the mechanism by which abGCs contribute to AD action remains unknown. During their maturation process, these immature neurons exhibit unique properties that could underlie their ability to influence behavioral output. In particular, abGCs in the DG exhibit a period of heightened plasticity 4–6 weeks after birth that is mediated by GluN2B-expressing NMDA receptors. The functional contribution of this critical window to AD responsiveness is unclear. Here, we determined the behavioral and neurogenic responses to the AD fluoxetine (FLX) in mice lacking GluN2B-containing NMDA receptors in abGCs. We found that these mice exhibited an attenuated response to FLX in a neurogenesis-dependent behavioral assay of FLX action, while neurogenesis-independent behaviors were unaffected by GluN2B deletion. In addition, deletion of GluN2B attenuated FLX-induced increases in dendritic complexity of abGCs suggesting that the blunted behavioral efficacy of FLX may be caused by impaired differentiation of young abGCs.
Highlights
Adult hippocampal neurogenesis is a process that results in the generation of new neurons in the dentate gyrus (DG) throughout life (Gross, 2000; Kempermann et al, 2015)
We show that deletion of the GluN2B subunit significantly attenuates a neurogenesis-dependent behavioral response to FLX, and may block FLX’s ability to enhance young adult-born granule cells (abGCs)’ maturation and subsequent integration into the hippocampal network
TMX injection in adult mice leads to deletion of GluN2B and expression of YFP in neural precursor cells (NPCs) and their subsequent progeny
Summary
Adult hippocampal neurogenesis is a process that results in the generation of new neurons in the dentate gyrus (DG) throughout life (Gross, 2000; Kempermann et al, 2015). Increases in proliferation and survival have been observed leading to an overall increase in the number of adult-born granule cells (abGCs) integrating into the hippocampal circuit (Malberg et al, 2000; Santarelli et al, 2003; Encinas et al, 2006; Wang et al, 2008; David et al, 2009) Maturation of these abGCs is enhanced, as is a neurogenesis-dependent form of long-term potentiation (LTP) in the DG evoked by medial perforant path stimulation under intact.
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