Ablation of hippocampal neurogenesis in mice impairs the response to stress during the dark cycle

Abstract

The functional role of adult neurogenesis in the hippocampus remains the subject of intense speculation. One recent hypothesis is that adult-born neurons contribute to the endocrine and behavioural outputs of the stress response. Here we show a genetic model system to ablate neurogenesis by inducibly deleting Tbr2 gene function specifically in the hippocampus and corroborate our findings in a radiation-based model of neurogenesis deprivation. We found that mice with ablation of new neurons in the dentate gyrus exhibit reduced anxiety during the dark cycle. After restraint stress, corticosterone levels in neurogenesis-deficient mice decreased more quickly than controls and were more sensitive to suppression by dexamethasone. Furthermore, glucocorticoid receptor target genes and neuronal activity markers showed reduced expression after stress in neurogenesis-deficient mice. These findings suggest that newborn neurons in the hippocampus are involved in sensing and eliciting an appropriate response to stress.

Differential expression of a stress‐regulated gene Nr4a2 characterizes early‐ and late‐born hippocampal granule cells

“…Alternatively, differential responses to stress exposure between the two populations, as represented by Nr4a expression, might be involved in the proposed functions of adult neurogenesis such as fearassociated learning or HPA axis regulation (Anacker & Hen, 2017;Snyder, Soumier, Brewer, Pickel, & Cameron, 2011;Tsai, Tsai, Arnold, & Huang, 2015). There is substantial evidence that hippocampal Nr4a2 expression plays a role in learning (Hawk et al, 2012).…”

“…Although the functional role of adult hippocampal neurogenesis is still a matter of debate, one leading hypothesis is that relatively high excitability of newly generated cells contributes to learning and memory processes (Clelland et al, 2009;Deng, Aimone, & Gage, 2010). New GCs lose excitability as they mature by developing GABAnergic inhibition and become physiologically indistinguishable from the preexisting population (by 2 months after cell birth in mice; Ge et al, 2006;van Praag et al, 2002). Although adult-generated GCs preferentially locate in the inner side of the GC layer and their morphological maturation is delayed compared to their developmental counterparts (Crespo, Stanfield, & Cowan, 1986;Kempermann, Gast, Kronenberg, Yamaguchi, & Gage, 2003;Zhao, Teng, Summers Jr., Ming, & Gage, 2006), it remains largely unclear whether any functional and/or phenotypic difference exists to differentiate between early-and lateborn GC populations over long periods.…”

Re-evaluating the link between neuropsychiatric disorders and dysregulated adult neurogenesis

“…One clue to a potential underlying mechanism is that new neurons buffer the body’s stress axis responsiveness and associated behaviors 62,107 . For example, a loss of new neurons results in a hyperactive stress response in mice 62 .…”

Topological Weyl semimetals in the chiral antiferromagnetic materials Mn3Ge and Mn3Sn

“…Currently discovered WSM materials can be classified into two groups. One group breaks crystal inversion symmetry but preserves time-reversal symmetry (e.g., TaAs-family transition-metal pnictides [18,19] and WTe 2 -and MoTe 2 -family transition-metal dichalcogenides [20][21][22][23][24][25][26]). The other group breaks time-reversal symmetry in ferromagnets with possible tilted moments (e.g., magnetic Heusler GdPtBi [27,28] and YbMnBi 2 [29]).…”