Neurons in very few CNS populations continue to be produced during adulthood. The goal of our research is to understand the function of this adult neurogenesis by studying the regulation of neuronal precursor proliferation and survival in the dentate gyrus, a part of the hippocampal region in which large numbers of new neurons are born throughout adulthood. This year we completed an investigation of the naturally occurring death of newborn granule neurons in the adult dentate gyrus. Previous reports suggested that many of the newborn granule neurons disappear shortly after being born, but it was unclear whether this disappearance was actually due to cell death or simply to loss of the marker used to identify them. Additionally, it was unclear whether loss of cells continued until all new cells were gone, resulting in a fairly short lifespan for these neurons. Our work showed that nearly half of all the new granule cells in the adult dentate gyrus normally die within 4 weeks of being born. However, after this 4-week time point we saw no further death of the now mature granule neurons. This finding indicates that the cell death is likely to reflect a normal part of the development of new granule cells and suggests a competitive process through which neurons in functional or ?useful? circuits survive while cells that do not become integrated into functional circuits die. We compared the survival of newborn granule neurons in the adult rat to that of newborn granule neurons during the peak of dentate gyrus development during the first two postnatal weeks. We found that the survival rate of immature neurons was virtually identical in development and in adulthood. However, while the adult-born neurons stop dying after 4 weeks, those born in development continue to die at a slow but steady rate. This difference in late susceptibility of granule cells born at different times suggests that granule cells born during early postnatal development, when the rat has limited interaction with the environment may be preferentially replaced by neurons born in adulthood when the rat has more complex interaction with the environment and a fully-functional hippocampus.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Intramural Research (Z01)
Project #
1Z01MH002784-02
Application #
6824235
Study Section
(IRP)
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2003
Total Cost
Indirect Cost
Name
U.S. National Institute of Mental Health
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Snyder, Jason S; Soumier, Amélie; Brewer, Michelle et al. (2011) Adult hippocampal neurogenesis buffers stress responses and depressive behaviour. Nature 476:458-61
Mozhui, Khyobeni; Karlsson, Rose-Marie; Kash, Thomas L et al. (2010) Strain differences in stress responsivity are associated with divergent amygdala gene expression and glutamate-mediated neuronal excitability. J Neurosci 30:5357-67
Snyder, Jason S; Glover, Lucas R; Sanzone, Kaitlin M et al. (2009) The effects of exercise and stress on the survival and maturation of adult-generated granule cells. Hippocampus 19:898-906
Snyder, Jason S; Choe, Jessica S; Clifford, Meredith A et al. (2009) Adult-born hippocampal neurons are more numerous, faster maturing, and more involved in behavior in rats than in mice. J Neurosci 29:14484-95
Snyder, Jason S; Radik, Ruvim; Wojtowicz, J Martin et al. (2009) Anatomical gradients of adult neurogenesis and activity: young neurons in the ventral dentate gyrus are activated by water maze training. Hippocampus 19:360-70
Yang, Rebecca J; Mozhui, Khyobeni; Karlsson, Rose-Marie et al. (2008) Variation in mouse basolateral amygdala volume is associated with differences in stress reactivity and fear learning. Neuropsychopharmacology 33:2595-604
Norcross, Maxine; Mathur, Poonam; Poonam, Mathur et al. (2008) Effects of adolescent fluoxetine treatment on fear-, anxiety- or stress-related behaviors in C57BL/6J or BALB/cJ mice. Psychopharmacology (Berl) 200:413-24
Karlsson, Rose-Marie; Choe, Jessica S; Cameron, Heather A et al. (2008) The neuropeptide Y Y1 receptor subtype is necessary for the anxiolytic-like effects of neuropeptide Y, but not the antidepressant-like effects of fluoxetine, in mice. Psychopharmacology (Berl) 195:547-57
Cameron, Heather A; Dayer, Alexandre G (2008) New interneurons in the adult neocortex: small, sparse, but significant? Biol Psychiatry 63:650-5
Olariu, Ana; Cleaver, Kathryn M; Cameron, Heather A (2007) Decreased neurogenesis in aged rats results from loss of granule cell precursors without lengthening of the cell cycle. J Comp Neurol 501:659-67

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