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The CREB/CREM Transcription Factors Negatively Regulate Early Synaptogenesis and Spontaneous Network Activity

  1. Eduardo Soriano1
  1. 1Institute for Research in Biomedicine, Department of Cell Biology, and Centro de Investigación Biomédica en Red para Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, University of Barcelona, 08028 Barcelona, Spain, and
  2. 2Molecular Biology of the Cell I, German Cancer Research Center, 69120 Heidelberg, Germany
  1. Correspondence should be addressed to Dr. Eduardo Soriano, Institute for Research in Biomedicine, Barcelona Science Park, Lab A1-S1, University of Barcelona, Baldiri Reixac 10, 08028 Barcelona, Spain. eduardo.soriano{at}irbbarcelona.org
  1. ↵*F.A., C.D.-R., and R.P. contributed equally to this work.

Abstract

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 CREB1NescreCREM−/− (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.

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