GABA-cAMP response element-binding protein signaling regulates maturation and survival of newly generated neurons in the adult hippocampus.
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.
Jagasia
Ravi
R
Research Group/Adult Neural Stem Cells and Neurogenesis, Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Munich-Neuherberg, Germany.
Steib
Kathrin
K
Englberger
Elisabeth
E
Herold
Sabine
S
Faus-Kessler
Theresa
T
Saxe
Michael
M
Gage
Fred H
FH
Song
Hongjun
H
Lie
D Chichung
DC
D000818:Animals; D001973:Bromodeoxyuridine; D002470:Cell Survival / Q000502:physiology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism* / Q000502:physiology; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005260:Female; D005838:Genotype; D006624:Hippocampus / Q000166:cytology* / Q000502:physiology; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism* / Q000502:physiology; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism* / Q000502:physiology; D010766:Phosphorylation; D012190:Retroviridae / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014162:Transfection / Q000379:methods; D005680:gamma-Aminobutyric Acid / Q000378:metabolism* / Q000502:physiology
D017362:Cyclic AMP Response Element-Binding Protein; C000714847:Dcx protein, mouse; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D005680:gamma-Aminobutyric Acid; D001973:Bromodeoxyuridine