The CREB/CREM transcription factors negatively regulate early synaptogenesis and spontaneous network activity.
The family of CREB (cAMP response element-binding protein) transcription factors are involved in a variety of biological processes including the development and plasticity of the nervous system. In the maturing and adult brain, CREB genes are required for activity-dependent processes, including synaptogenesis, refinement of connections and long-term potentiation. Here, we use CREB1(Nescre)CREM(-/-) (cAMP-responsive element modulator) mutants to investigate the role of these genes in stimulus-independent patterns of neural activity at early stages. We show that lack of CREB/CREM genes specifically in neural tissue leads to increased synaptogenesis and to a dramatic increase in the levels of spontaneous network activity at embryonic stages. Thus, the functions of CREB/CREM genes in neural activity differ in distinct periods of neural development.
Aguado
Fernando
F
Department of Cell Biology, Centro de Investigación Biomédica en Red para Enfermedades Neurodegenerativas, Institute for Research in Biomedicine, University of Barcelona, Barcelona, Spain.
Díaz-Ruiz
Carmen
C
Parlato
Rosanna
R
Martínez
Albert
A
Carmona
Maria A
MA
Bleckmann
Susanne
S
Ureña
Jesús M
JM
Burgaya
Ferran
F
del Río
Jose A
JA
Schütz
Günther
G
Soriano
Eduardo
E
D000367:Age Factors; D000818:Animals; D001921:Brain / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D051786:Cyclic AMP Response Element Modulator / Q000172:deficiency / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000172:deficiency / Q000502:physiology*; D004622:Embryo, Mammalian; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D009434:Neural Pathways / Q000502:physiology* / Q000648:ultrastructure; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure; D013569:Synapses / Q000235:genetics* / Q000648:ultrastructure
C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D051786:Cyclic AMP Response Element Modulator; D002118:Calcium