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The Journal of Neuroscience, February 22, 2006, 26(8):2326-2334; doi:10.1523/JNEUROSCI.4111-05.2006

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Development/Plasticity/Repair
Delayed Development of Adult-Generated Granule Cells in Dentate Gyrus

Linda S. Overstreet-Wadiche, AeSoon L. Bensen, and Gary L. Westbrook

Vollum Institute, L474, Oregon Health & Science University, Portland, Oregon 97239

Correspondence should be addressed to Linda S. Overstreet-Wadiche, Overstreet-Wadiche, Vollum Institute, L474, Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239. Email: overstre{at}ohsu.edu

A substantial fraction of adult-generated granule cells in the dentate gyrus survive and integrate into the existing neuronal network. These newborn neurons must navigate the environment of the adult brain, a setting that is presumably less optimized for neuronal maturation compared with that in the developing brain. We used EGFP (enhanced green fluorescent protein) expression in newborn granule cells to compare the maturation of adult-generated granule cells to those generated in neonates. Labeled newborn granule cells had indistinguishable physiological properties in adults and neonates, indicating they were at the same functional stage. However, the maturation of adult-generated granule cells was slower than neonatal-generated granule cells. Depolarizing GABAergic network activity and transcription factor activation were reduced in adults relative to neonates, suggesting a role for neural activity in the maturation of newborn granule cells. Consistent with this idea, maturation was altered in mice lacking the GABA synthetic enzyme GAD65 (glutamic acid decarboxylase 65). Together, these results provide evidence that activity-dependent processes in the local environment influence the maturation of newborn granule cells.

Key words: granule cell; depolarizing GABA; development; giant depolarizing potential; activity dependent; neural stem cell; neurogenesis; dentate gyrus; bromodeoxyuridine; hippocampus; GAD65

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Received July 5, 2005; revised Jan. 13, 2006; accepted Jan. 14, 2006.

Correspondence should be addressed to Linda S. Overstreet-Wadiche, Overstreet-Wadiche, Vollum Institute, L474, Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239. Email: overstre{at}ohsu.edu

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