Rapid extension of axons into the CA3 region by adult-generated granule cells

Abstract

The dentate gyrus continues to produce granule neurons throughout adulthood. The present study examined the extension of axons by adult-generated granule neurons into hippocampal area CA3. We injected the fluorescent retrograde tracers Fast blue (FB) and FluoroRuby (FR) into area CA3 of adult male rats at various times after the administration of 5Ј-bromo-2Ј-deoxyuridine (BrdU), a marker of proliferating cells and their progeny. We report that immature granule cells extend axons into CA3 as rapidly as 4-10 days after mitosis. A significant increase in the percentage of BrdU-labeled cells that were labeled with FB or FR was observed by 2 weeks after BrdU administration. This proportion remained roughly constant up to 3 weeks after BrdU-labeling, a time at which markers of a mature neuronal phenotype are expressed. BrdU-labeled cells that contained either FB or FR often were located far from the tracer injection site, indicating that these cells had extended relatively long axons. Collectively these results suggest that adult-generated granule neurons may influence normal hippocampal function, even at a very early stage after their production. J.

Genetic Regulation of Behavioral and Neuronal Responses to Fluoxetine

“…In the adult mammalian brain, neurogenesis is largely restricted to the olfactory bulbs and the subgranular zone (SGZ) of the hippocampus, a region lined with serotonergic fibers (Kaplan and Hinds, 1977). Approximately 250 000 new neurons are born monthly in the SGZ of the adult rat, 50-70% of which differentiate into neurons that migrate into the granule cell layer (Hastings and Gould, 1999;Cameron and McKay, 2001). Antidepressants have been shown to increase both proliferation and survival of hippocampal neurons under basal conditions: in the hippocampus of unstressed mice, chronic antidepressant treatment results in a 60% increase in BrdU labeling (Santarelli et al, 2003).…”

Cell Proliferation is Influenced by Bulbectomy and Normalized by Imipramine Treatment in a Region-Specific Manner

“…Throughout life, neural stem cells continue to proliferate and produce neurons and glia in the hippocampal dentate gyrus and in the subventricular zone (SVZ) of the lateral ventricle (Schaffer and Gage, 2004). Immature neurons in the subgranular zone of the hippocampus migrate into the granule cell layer (Hastings and Gould, 1999), where they differentiate and appear to have morphological and physiological characteristics that are similar to adult granule cells (van Praag et al, 2002). Precursors of the anterior SVZ migrate through the rostral migratory stream (RMS) into the core of the olfactory bulb.…”

Manipulation of Neural Precursors in situ Induction of Neurogenesis in the Neocortex of Adult Mice

“…Adult-born hippocampal granule neurons are morphologically indistinguishable from surrounding granule neurons . The precursor cells appear to mature rapidly, and they extend their processes into the CA3 region as early as four days after division (Hastings and Gould 1999). The properties of both the precursor cells and the hippocampal environment likely contribute to the rapid maturation observed.…”

“…Newborn cells destined to become neurons are generated along the innermost aspect of the granule cell layer, the subgranular zone, of the dentate gyrus of the adult hippocampus. The cells migrate a short distance into the granule cell layer, send dendrites into the molecular layer of the hippocampus, and send their axons into the CA3 region of the hippocampus (Stanfield and Trice 1988;Markakis and Gage 1999;Hastings and Gould 1999). Adult-born hippocampal granule neurons are morphologically indistinguishable from surrounding granule neurons .…”