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The Journal of Neuroscience, November 2, 2005, 25(44):10105-10118; doi:10.1523/JNEUROSCI.3512-05.2005

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Development/Plasticity/Repair
cAMP Response Element-Binding Protein Regulates Differentiation and Survival of Newborn Neurons in the Olfactory Bulb

Claudio Giachino,¹ Silvia De Marchis,¹ Costanza Giampietro,¹ Rosanna Parlato,² Isabelle Perroteau,¹ Günther Schütz,² Aldo Fasolo,^1,3 and Paolo Peretto¹

¹Department of Animal and Human Biology, University of Turin, 10123 Turin, Italy, ²German Cancer Research Center, D-69120 Heidelberg, Germany, and ³Rita Levi Montalcini Center for Brain Repair, University of Turin, 10125 Turin, Italy

The transcription factor cAMP response element-binding protein (CREB) is involved in multiple aspects of neuronal development and plasticity. Here, we demonstrate that CREB regulates specific phases of adult neurogenesis in the subventricular zone/olfactory bulb (SVZ/OB) system. Combining immunohistochemistry with bromodeoxyuridine treatments, cell tracer injections, cell transplants, and quantitative analyses, we show that although CREB is expressed by the SVZ neuroblasts throughout the neurogenic process, its phosphorylation is transient and parallels neuronal differentiation, increasing during the late phase of tangential migration and decreasing after dendrite elongation and spine formation. In vitro, inhibition of CREB function impairs morphological differentiation of SVZ-derived neuroblasts. Transgenic mice lacking CREB, in a null CREM genetic background, show reduced survival of newborn neurons in the OB. This finding is further supported by peripheral afferent denervation experiments resulting in downregulation of CREB phosphorylation in neuroblasts, the survival of which appears heavily impaired. Together, these findings provide evidence that CREB regulates differentiation and survival of newborn neurons in the OB.

Key words: subventricular zone; adult neurogenesis; cell differentiation; radial migration; cell survival; olfactory deafferentation

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Received Jan 20, 2005; accepted September 9, 2005.

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