When is adult hippocampal neurogenesis necessary for learning? Evidence from animal research

Departamento de Psicobiología y Metodología de las CC, Universidad de Málaga, Campus de Teatinos, E-29071 Málaga, Spain.
Reviews in the neurosciences (Impact Factor: 3.33). 06/2011; 22(3):267-83. DOI: 10.1515/RNS.2011.027
Source: PubMed


The hippocampus is a key brain structure involved in the short- and long-term processing of declarative memory. Since adult hippocampal neurogenesis was first found, numerous studies have tried to establish the contribution of newborn neurons to hippocampus-dependent cognitive functions. However, this large amount of research has generated contradictory results. In this paper, we review the body of evidence investigating the relationship between hippocampal neurogenesis and learning to conclude the functional role of adult-born hippocampal neurons. First, factors that could explain discrepancies among experiments are taken into account. Then, in addition to methodological differences, we emphasize the importance of the age of the newborn neurons studied, as to how their maturation influences both their properties and potential functionality. Next, we discuss which declarative memory components could require involvement of adult hippocampal neurogenesis, taking into consideration the representational demands of the task, its difficulty and the level of performance reached by the subject. Finally, other factors that could modulate neurogenesis and memory, such as stress levels or previous experience of the animal, should also be taken into consideration in interpreting experiments focused on neurogenesis. In conclusion, our analysis of published studies suggests that new adult-born neurons, under certain circumstances, have a crucial and irreplaceable role in hippocampal learning.

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Available from: Guillermo Estivill-Torrús, Apr 09, 2015
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    • "Moreover, GSK-3β dysregulation is associated with the pathogenesis of many neuropsychiatric disorders, including dementia (Hernandez et al., 2002; Hooper et al., 2008; Giese, 2009). On the other hand, deficits of hippocampal-dependent memory, including contextual fear conditioning , are linked to impaired adult neurogenesis (Deng et al., 2010; Castilla-Ortega et al., 2011; Pan et al., 2012). Valproic acid (VPA) is an effective anti-epileptic drug, which has been also used for many years as a mood-stabilizing agent for treatment of psychiatric disorders. "
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    ABSTRACT: Valproic acid (VPA), a long-standing anti-epileptic and anti-manic drug, exerts multiple actions in the nervous system through various molecular mechanisms. Neuroprotective properties have been attributed to VPA in different models of neurodegeneration, but contrasting results on its improvement of learning and memory have been reported in non-pathologic conditions. In the present study, we have tested on a hippocampal-dependent learning test, the contextual fear conditioning, the effect of chronic VPA administration through alimentary supplementation that allows relatively steady concentrations to be reached by a drug otherwise very rapidly eliminated in rodents. Contextual fear memory was significantly impaired in rats chronically treated with VPA for 4weeks. To understand the cellular and molecular correlates of this amnesic effect with particular regard to hippocampus, we addressed three putatively memory-related targets of VPA action in this brain area, obtaining the following main results: i) chronic VPA promoted an increase of post-translational modifications of histone H3 (acetylation and phosphorylation) known to favor gene transcription; ii) adult neurogenesis in the dentate gyrus, which has been controversially reported to be affected by VPA, was unchanged; iii) GSK-3β, a kinase playing a key role in hippocampal plasticity, as well as in learning and memory, was dysregulated by VPA treatment. These results point at GSK-3β dysregulation in the hippocampus as an important parameter in the amnesic effect of VPA. The VPA amnesic effect in the animal model here reported is also supported by some observations in patients and, therefore, it should be taken into account and monitored in VPA-based therapies.
    Pharmacology Biochemistry and Behavior 03/2013; 106. DOI:10.1016/j.pbb.2013.02.013 · 2.78 Impact Factor
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    • "Cell proliferation and neurogenesis have also recently been described as a necessary component of learning and memory in several taxa (Castilla-Ortega et al., 2011; Nogues et al., 2011). Because the males used in our study had all previously been dominant, and this species can reversibly switch between social states depending on the composition of the social environment, the ascension to dominance also likely involves neuronal circuitry involved in learning and memory, and reward pathways. "
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    ABSTRACT: New cells are added in the brains of all adult vertebrates, but fishes have some of the greatest potential for neurogenesis and gliogenesis among all taxa, partly due to their indeterminate growth. Little is known, however, about how social interactions influence cell proliferation in the brain of these fishes that comprise the largest group of vertebrates. We used 5-bromo-2'-deoxyuridine (BrdU) to identify and localize proliferation zones in the telencephalon, diencephalon, mesencephalon, and rhombencephalon that were primarily associated with ventricular surfaces in the brain of the African cichlid fish Astatotilapia burtoni. Cell migration was evident in some regions by 1 day post injection, and many newborn cells coexpressed the neuronal marker HuC/D at 30 days, suggesting they had differentiated into neurons. To test the hypothesis that social status and perception of an opportunity to rise in rank influenced cell proliferation, we compared numbers of BrdU-labeled cells in multiple brain nuclei among fish of different social status. Socially suppressed subordinate males had the lowest numbers of proliferating cells in all brain regions examined, but males that were given an opportunity to rise in status had higher cell proliferation rates within 1 day, suggesting rapid upregulation of brain mitotic activity associated with this social transition. Furthermore, socially isolated dominant males had similar numbers of BrdU-labeled cells compared with dominant males that were housed in a socially rich environment, suggesting that isolation has little effect on proliferation and that reduced proliferation in subordinates is a result of the social subordination. These results suggest that A. burtoni will be a useful model to analyze the mechanisms of socially induced neurogenesis in vertebrates.
    The Journal of Comparative Neurology 10/2012; 520(15):3471-91. DOI:10.1002/cne.23100 · 3.23 Impact Factor
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    • "A thin zone of self-renewing progenitor cells located within the subgranular zone (SGZ) continuously seeds the dentate gyrus with new cells (Alvarez-Buylla and Lim 2004; Aimone et al. 2006; Ming and Song 2011). A subset of these cells develop into adult granule cells that extend apical dendrites into the molecular layer, synapse on pyramidal cells of layer CA3, and contribute to hippocampal-dependent processes, such as learning and memory (Deng et al. 2010; Castilla-Ortega et al. 2011; Koehl and Abrous 2011). "
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    ABSTRACT: The neurogenic niche within the subgranular zone (SGZ) of the dentate gyrus is a source of new neurons throughout life. Interestingly, SGZ proliferative capacity is regulated by both physiological and pathophysiological conditions. One outstanding question involves the molecular mechanisms that regulate both basal and inducible adult neurogenesis. Here, we examined the role of the MAPK-regulated kinases, mitogen- and stress-activated kinase (MSK)1 and MSK2. as regulators of dentate gyrus SGZ progenitor cell proliferation and neurogenesis. Under basal conditions, MSK1/2 null mice exhibited significantly reduced progenitor cell proliferation capacity and a corollary reduction in the number of doublecortin (DCX)-positive immature neurons. Strikingly, seizure-induced progenitor proliferation was totally blocked in MSK1/2 null mice. This blunting of cell proliferation in MSK1/2 null mice was partially reversed by forskolin infusion, indicating that the inducible proliferative capacity of the progenitor cell population was intact. Furthermore, in MSK1/2 null mice, DCX-positive immature neurons exhibited reduced neurite arborization. Together, these data reveal a critical role for MSK1/2 as regulators of both basal and activity-dependent progenitor cell proliferation and morphological maturation in the SGZ.
    Journal of Neurochemistry 09/2012; 123(5). DOI:10.1111/jnc.12035 · 4.28 Impact Factor
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