Adult-Born Hippocampal Neurons Are More Numerous, Faster Maturing, and More Involved in Behavior in Rats than in Mice

Unit on Neuroplasticity, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 11/2009; 29(46):14484-95. DOI: 10.1523/JNEUROSCI.1768-09.2009
Source: PubMed


Neurons are born throughout adulthood in the hippocampus and show enhanced plasticity compared with mature neurons. However, there are conflicting reports on whether or not young neurons contribute to performance in behavioral tasks, and there is no clear relationship between the timing of maturation of young neurons and the duration of neurogenesis reduction in studies showing behavioral deficits. We asked whether these discrepancies could reflect differences in the properties of young neurons in mice and rats. We report that young neurons in adult rats show a mature neuronal marker profile and activity-induced immediate early gene expression 1-2 weeks earlier than those in mice. They are also twice as likely to escape cell death, and are 10 times more likely to be recruited into learning circuits. This comparison holds true in two different strains of mice, both of which show high rates of neurogenesis relative to other background strains. Differences in adult neurogenesis are not limited to the hippocampus, as the density of new neocortical neurons was 5 times greater in rats than in mice. Finally, in a test of function, we find that the contribution of young neurons to fear memory is much greater in rats than in mice. These results reveal substantial differences in new neuron plasticity and function between these two commonly studied rodent species.

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Available from: Jason Snyder, Jul 22, 2014
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    • "l . , 2002 ) of adult - born neurons 1 – 2 weeks old at the start of training but induce death of neurons less than 7 days old at the start of training ( Ambrogini et al . , 2000 , 2004 ; Döbrössy et al . , 2003 ; Ehninger and Kempermann , 2006 ; Dupret et al . , 2007 ) . The pace of neuronal maturation is 1 – 2 weeks faster in rats than in mice ( Snyder et al . , 2009a ) ; thus , learning - induced apoptosis in mice would be predicted to occur in cells 2 – 3 weeks of age , which corresponds to the period during which zif268 suppression was observed . Targets of zif268 include activity - induced neurotrophic factors such as BDNF , which are important in neuronal growth and survival ( Baumgärtel et al ."
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    ABSTRACT: Thousands of neurons are born each day in the dentate gyrus (DG), but many of these cells die before reaching maturity. Both death and survival of adult-born neurons are regulated by neuronal activity in the DG. The immediate-early gene (IEG) zif268 appears to be an important mediator of these effects, as its expression can be induced by neural activity and knockout of zif268 impairs survival of adult-born neurons (Richardson et al., 1992; Veyrac et al., 2013). Despite the apparent importance of zif268 for adult neurogenesis, its behavior-induced expression has not been fully characterized in adult-born neurons. Here we characterize behavior-evoked expression of zif268 in mature and newborn dentate granule cells (DGCs). We first quantified zif268 expression in doublecortin-positive (DCX+) immature neurons and in the general granule cell population after brief exposure to a novel environment (NE). In the general granule cell population, zif268 expression peaked 1 h after NE exposure and returned to baseline by 8 h post-exposure. However, in the DCX+ cells, zif268 expression was suppressed relative to home cage for at least 8 h post-exposure. We next asked whether suppression of zif268 in DCX+ immature cells occurs in other behavioral paradigms that recruit the hippocampus. Exposure to Morris water maze (MWM) training, an enriched environment, or a NE caused approximately equal suppression of zif268 expression in DCX+ cells and approximately equal activation of zif268 expression among the general granule cell population. The same behavioral procedures activated zif268 expression in 6-week-old BrdU-labeled adult-born neurons, indicating that zif268 suppression is specific to immature neurons. Finally, we asked whether zif268 suppression varied as a function of age within the DCX+ population, which ranges in age from 0 to approximately 4 weeks. NE exposure had no significant effect on zif268 expression in 2- or 4-week-old BrdU-labeled neurons, but it significantly suppressed zif268 expression in 3-week-old neurons. In summary, behavioral experience transiently activated expression of zif268 in mature granule cells but caused a more long-lasting suppression of zif268 expression in immature, adult-born granule cells. We hypothesize that zif268 suppression inhibits memory-related synaptic plasticity in immature neurons or mediates learning-induced apoptosis of immature adult-born neurons.
    Frontiers in Systems Neuroscience 09/2015; 9:118. DOI:10.3389/fnsys.2015.00118
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    • "y until 35 dpi and a constant number of surviving cells at 49 , 63 , and 77 dpi ( Fig 2C ) . Our results are in line with previous findings that demonstrated a 70% decrease in BrdU+ cell number between 1 and 4 weeks following BrdU injection in mice . The number of surviving cells was not further reduced at 10 weeks following BrdU treatment [ 6 ] . Snyder et al . ( 2009 ) have established the rate of newborn cell loss over time in the mouse based on stereo - logical analyses , a method that takes hippocampal volume changes into account , and enables generation of absolute cell numbers [ 6 ] . Nevertheless , our results based on relative cell numbers are consistent with this work . This further supports "
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    ABSTRACT: Adult neurogenesis is frequently studied in the mouse hippocampus. We examined the morphological development of adult-born, immature granule cells in the suprapyramidal blade of the septal dentate gyrus over the period of 7-77 days after mitosis with BrdU-labeling in 6-weeks-old male Thy1-GFP mice. As Thy1-GFP expression was restricted to maturated granule cells, it was combined with doublecortin-immunolabeling of immature granule cells. We developed a novel classification system that is easily applicable and enables objective and direct categorization of newborn granule cells based on the degree of dendritic development in relation to the layer specificity of the dentate gyrus. The structural development of adult-generated granule cells was correlated with age, albeit with notable differences in the time course of development between individual cells. In addition, the size of the nucleus, immunolabeled with the granule cell specific marker Prospero-related homeobox 1 gene, was a stable indicator of the degree of a cell's structural maturation and could be used as a straightforward parameter of granule cell development. Therefore, further studies could employ our doublecortin-staging system and nuclear size measurement to perform investigations of morphological development in combination with functional studies of adult-born granule cells. Furthermore, the Thy1-GFP transgenic mouse model can be used as an additional investigation tool because the reporter gene labels granule cells that are 4 weeks or older, while very young cells could be visualized through the immature marker doublecortin. This will enable comparison studies regarding the structure and function between young immature and older matured granule cells.
    PLoS ONE 08/2015; 10(8):e0135493. DOI:10.1371/journal.pone.0135493 · 3.23 Impact Factor
    • "ation as only young adult - born neurons are recruited for pattern sepa - ration , whereas 6 weeks or older adult - born and developmental - born neurons do not play a role for pattern separation in mice ( Nakashiba et al . , 2012 ) . Maturation of adult - born neurons differs between mice and rats , and is faster in rats when compared with mice ( Snyder et al . , 2009 ) . Therefore , 4 - week - old dentate granule neurons in rats in the current study may not play a large role for pattern separation . More research examining shorter timelines for BrdU / zif268 coexpression after a pattern separation task are needed to determine the timing of when new neurons are activated in response to pattern separa"
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    ABSTRACT: Adult neurogenesis in the dentate gyrus (DG) plays a crucial role for pattern separation and there are sex differences in the regulation of neurogenesis. Although sex differences, favoring males, in spatial navigation have been reported, it is not known whether there are sex differences in pattern separation. The current study was designed to determine whether there are sex differences in the ability for separating similar or distinct patterns, learning strategy choice, adult neurogenesis and immediate early gene (IEG) expression in the DG in response to pattern separation training. Male and female Sprague-Dawley rats received a single injection of the DNA synthesis marker, bromodeoxyuridine (BrdU) and were tested for the ability of separating spatial patterns in a spatial pattern separation version of delayed nonmatching to place task using the 8-arm radial arm maze. Twenty eight days following BrdU injection, rats received a probe trial to determine whether they were idiothetic or spatial strategy users. We found that male spatial strategy users outperformed female spatial strategy users only when separating similar, but not distinct, patterns. Furthermore male spatial strategy users had greater neurogenesis in response to pattern separation training than all other groups. Interestingly neurogenesis was positively correlated with performance on similar pattern trials during pattern separation in female spatial strategy users but negatively correlated with performance in male idiothetic strategy users. These results suggest that the survival of new neurons may play an important positive role for pattern separation of similar patterns in females. Furthermore, we found sex and strategy differences in IEG expression in the CA1 and CA3 regions in response to pattern separation. These findings emphasize the importance of studying biological sex on hippocampal function and neural plasticity. This article is protected by copyright. All rights reserved.
    Hippocampus 07/2015; DOI:10.1002/hipo.22493 · 4.16 Impact Factor
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