A simplified model of Rac1 signaling and function in learning-induced adult neurogenesis. Loss of Rac1 function in the mature neurons of the granule cell layer changes synaptic plasticity and impairs activity-induced transcriptional changes such as the upregulation of Gadd45b and BDNF. These transient changes in the mature neurons lead to long-lasting modifications of adult neurogenesis. Neuronal activation of mature dentate granule cells induces Rac1 activity through the NMDA receptor and the TrkB receptor. Rac1 triggers activation of multiple downstream pathways including (1) the mitogen activate protein MAPK pathway, which induces expression of TGF-β1 and BDNF via c-Jun and CREB, respectively and (2) the STAT/NFκB-Gadd45b pathway (Balliet et al., 2001; Hoffman and Liebermann, 2009) leading to BDNF expression (Ma et al., 2009a). Loss of Rac1 in mature neurons lowers learning-induced increases of Gadd45b and BDNF expression, but increases TGF-β1 expression. The secreted extrinsic factors from mature neurons in turn regulate several key aspects of adult neurogenesis over the long term. BDNF is known to promote proliferation, whereas TGF-β1 is known to upregulate p27 Kip1, which would lead to increased cell cycle exit within the NPC and reduce overall NPC proliferation (Kandasamy et al., 2010). NMDA receptor, N-methyl-d-aspartate receptor; TrkB, tropomyosin-related kinase B; MAPK, mitogen activate protein kinase family; CREB, cAMP response element-binding protein, Gadd45b, growth arrest and DNA-damage-inducible beta; p27 Kip1, cyclin-dependent kinase inhibitor p27; NFκB, nuclear factor κ-light-chain-enhancer of activated B-cells.