Neuroscience Bulletin

, Volume 30, Issue 4, pp 542-556

First online:

Activity-dependent signaling mechanisms regulating adult hippocampal neural stem cells and their progeny

  • Andrew J. CrowtherAffiliated withGraduate Program of Neurobiology Curriculum, University of North Carolina
  • , Juan SongAffiliated withDepartment of Pharmacology, University of North CarolinaNeuroscience Center/Neurobiology Curriculum, University of North CarolinaSchool of Medicine, University of North Carolina Email author 

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Adult neural stem cells (NSCs) reside in a restricted microenvironment, where their development is controlled by subtle and presently underexplored cues. This raises a significant question: what instructions must be provided by this supporting niche to regulate NSC development and functions? Signaling from the niche is proposed to control many aspects of NSC behavior, including balancing the quiescence and proliferation of NSCs, determining the cell division mode (symmetric versus asymmetric), and preventing premature depletion of stem cells to maintain neurogenesis throughout life. Interactions between neurogenic niches and NSCs also govern the homeostatic regulation of adult neurogenesis under diverse physiological, environmental, and pathological conditions. An important implication from revisiting many previously-identifi ed regulatory factors is that most of them (e.g., the antidepressant fluoxetine and exercise) affect gross neurogenesis by acting downstream of NSCs at the level of intermediate progenitors and neuroblasts, while leaving the NSC pool unaffected. Therefore, it is critically important to address how various niche components, signaling pathways, and environmental stimuli differentially regulate distinct stages of adult neurogenesis.


neural stem cell neuronal development neuronal plasticity