GABA-CREB signalling regulates maturation and survival of newly generated neurons in the adult hippocampus

By R. Jagasia, K. Steib, E. Englberger, S. Herold, T. Faus‐Kessler, M. Saxe, Fred H. Gage, Hongjun Song, D. C. Lie. 2009

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Survival and integration of new neurons in the hippocampal circuit are rate-limiting steps in adult hippocampal neurogenesis. Neuronal network activity is a major regulator of these processes, yet little is known about the respective downstream signaling pathways. Here, we investigate the role of cAMP response element-binding protein (CREB) signaling in adult hippocampal neurogenesis. CREB is activated in new granule neurons during a distinct developmental period. Loss of CREB function in a cell-autonomous manner impairs dendritic development, decreases the expression of the neurogenic transcription factor NeuroD and of the neuronal microtubule-associated protein, doublecortin (DCX), and compromises the survival of newborn neurons. In addition, GABA-mediated excitation regulates CREB activation at early developmental stages. Importantly, developmental defects after loss of GABA-mediated excitation can be compensated by enhanced CREB signaling. These results indicate that CREB signaling is a central pathway in adult hippocampal neurogenesis, regulating the development and survival of new hippocampal neurons downstream of GABA-mediated excitation.

Subfields: Cellular and Molecular Neuroscience, Developmental Neuroscience, Genetics

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Citations in the corpus

Adult neurogenesis in brain repair: cellular plasticity vs. cellular replacement (2014, background): “…Transcription factor DG Quadrato et al., 2012 NF-KappaB p50 Transcription factor DG Denis-Donini et al., 2008 CREB Transcription factor DG Jagasia et al., 2009 Neuro D1 Transcription factor DG, SVZ Gao et al., 2009 PROX1 Transcription factor DG Lavado et al., 2010; Karalay et al., 2011”
Adult Neurogenesis in the Mammalian Brain: Significant Answers and Significant Questions (2011, background): “In the adult SGZ, GABA promotes dendritic growth, synapse formation, and survival of newborn neurons through CREB signaling (Jagasia et al., 2009).”
New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory? (2010, background): “The GABA-mediated activity seems to be important for the survival and maturation of adult-born DGCs: knockdown of SLC12A2 by RNA interference reduced the number of adult-born DGCs surviving the second week after birt”
Neuronal activity-dependent control of postnatal neurogenesis and gliogenesis (2018, neutral): “F or p er so na l u se o nl y. DG and promotes new neuron maturation (Tozuka et al. 2005), integration into local circuitry (Ge et al. 2006), and survival ( Jagasia et al. 2009).”
RBPJκ-Dependent Signaling Is Essential for Long-Term Maintenance of Neural Stem Cells in the Adult Hippocampus (2010, methodology): “…CRE-recombinase and Sox2, cDNAs for a CRE-recombinase carrying an additional nuclear localization signal (nls) (Kaspar et al., 2002) and murine Sox2 were cloned into the pCAG vector or the pCAG IRES-DSRED (Jagasia et al., 2009) to generate pCAGGFPnlsCRE (Tashiro et al., 2006) and pCAG-Sox2-DSRED.”
Maturation and integration of adult born hippocampal neurons: signal convergence onto small Rho GTPases (2013, background): “The effects of early GABAergic input on newborn neurons are likely mediated via cAMP response element-binding protein (CREB) signaling (Jagasia et al., 2009).”
The role of adult hippocampal neurogenesis in brain health and disease (2018, background): “A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript Table 1 Signals regulating adult hippocampal neurogenesis Stages Regulators Secreted factors and downstream effectors (Morphogens, growth fa”