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The Journal of Neuroscience, March 31, 2004, 24(13):3251-3259; doi:10.1523/JNEUROSCI.5173-03.2004
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Development/Plasticity/Repair
A Transgenic Marker for Newly Born Granule Cells in Dentate Gyrus
Linda S. Overstreet,1
Shane T. Hentges,1
Viviana F. Bumaschny,4
Flavio S. J. de Souza,4
James L. Smart,1
Andrea M. Santangelo,4
Malcolm J. Low,1,2,3
Gary L. Westbrook,1 and
Marcelo Rubinstein3,4,5
1Vollum Institute, 2Department of Behavioral Neuroscience, and 3The Center for Study of Weight Regulation and Associated Disorders, Oregon Health and Science University, Portland, Oregon 97239, 4Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, Consejo Nacional de Investigaciones Científicas y Técnicas, y Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, 1428 Buenos Aires, Argentina, and 5Centro de Estudios Científicos, Casilla 1469, Valdivia, Chile
Neurogenesis in the dentate gyrus continues into adulthood, yet little is known about the function of newly born neurons or how they integrate into an existing network of mature neurons. We made transgenic mice that selectively and transiently express enhanced green fluorescent protein (EGFP) in newly born granule cells of the dentate gyrus under the transcriptional control of proopiomelanocortin (POMC) genomic sequences. Analysis of transgenic pedigrees with truncation or deletion mutations indicated that EGFP expression in the dentate gyrus required cryptic POMC promoter regions dispensable for arcuate hypothalamic or pituitary expression. Unlike arcuate neurons, dentate granule cells did not express the endogenous POMC gene. EGFP-positive neurons had immature properties, including short spineless dendrites and small action potentials. Colocalization with bromodeoxyuridine indicated that EGFP-labeled granule cells were 2 weeks postmitotic. EGFP-labeled cells expressed markers for immature granule cells but not the glial marker GFAP. The number of EGFP-labeled neurons declined with age and increased with exercise, paralleling neurogenesis. Our results indicate that POMC-EGFP marks immature granule cells and that adult-generated granule cells integrate quite slowly into the hippocampal circuitry.
Key words: neurogenesis; neuronal progenitor; dentate granule cell; green fluorescent protein; transgenic mice; proopiomelanocortin; BrdU; PSA-nCAM
Received Nov 23, 2003;
revised February 17, 2004;
accepted February 18, 2004.
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