Adult-Generated Hippocampal Neurons Allow the Flexible Use of Spatially Precise Learning Strategies

By A. Garthe, J. Behr, Gerd Kempermann. 2009

611 citations recorded by the source corpus.

Despite enormous progress in the past few years the specific contribution of newly born granule cells to the function of the adult hippocampus is still not clear. We hypothesized that in order to solve this question particular attention has to be paid to the specific design, the analysis, and the interpretation of the learning test to be used. We thus designed a behavioral experiment along hypotheses derived from a computational model predicting that new neurons might be particularly relevant for learning conditions, in which novel aspects arise in familiar situations, thus putting high demands on the qualitative aspects of (re-)learning. In the reference memory version of the water maze task suppression of adult neurogenesis with temozolomide (TMZ) caused a highly specific learning deficit. Mice were tested in the hidden platform version of the Morris water maze (6 trials per day for 5 days with a reversal of the platform location on day 4). Testing was done at 4 weeks after the end of four cycles of treatment to minimize the number of potentially recruitable new neurons at the time of testing. The reduction of neurogenesis did not alter longterm potentiation in CA3 and the dentate gyrus but abolished the part of dentate gyrus LTP that is attributed to the new neurons. TMZ did not have any overt side effects at the time of testing, and both treated mice and controls learned to find the hidden platform. Qualitative analysis of search strategies, however, revealed that treated mice did not advance to spatially precise search strategies, in particular when learning a changed goal position (reversal). New neurons in the dentate gyrus thus seem to be necessary for adding flexibility to some hippocampus-dependent qualitative parameters of learning. Our finding that a lack of adult-generated granule cells specifically results in the animal's inability to precisely locate a hidden goal is also in accordance with a specialized role of the dentate gyrus in generating a metric rather than just a configurational map of the environment. The discovery of highly specific behavioral deficits as consequence of a suppression of adult hippocampal neurogenesis thus allows to link cellular hippocampal plasticity to well-defined hypotheses from theoretical models.

Subfields: Cognitive Neuroscience, Developmental Neuroscience, Neurology

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Citations in the corpus

The role of adult hippocampal neurogenesis in brain health and disease (2018, background): “Indeed, knocking down neurogenesis impairs reversal learning on the Morris water maze [65], active avoidance tasks [47, 66], and touchscreen-based location discrimination [67].”
Resolving new memories: a critical look at the dentate gyrus, adult neurogenesis, and pattern separation (2011, background): “Similarly, variability in apparatus settings and testing paradigms may have different demands for memory resolution, which could help explain the detection of behavioral phenotypes in some cases but not others (Dupret et al., 2008; Garthe et al., 2009; reviewed by Deng et al., 2010).”
Quiescent and active hippocampal neural stem cells with distinct morphologies respond selectively to physiological and pathological stimuli and aging. (2010, background): “In this respect, a fundamental question is: how much plasticity does the aged brain retain? Because DG neurogenesis actively contributes to memory and cognitive performance, which are heavily impaired during aging (Clelland et al., 2009; Garthe et al., 2009; Shors et al., 2001), it is critical to un”
Pattern separation: a common function for new neurons in hippocampus and olfactory bulb (2011, positive): “Recent studies showing a role for adult-born neurons in such tasks are consistent with the idea that neurogenesis contributes to pattern separation (Dupret et al., 2008; Garthe et al., 2009; Wojtowicz et al., 2008).”
Neurogenesis in the Adult Hippocampus. (2015, background): “, inhibited) conditions originates from the newborn neurons, which are not yet inhibited by the local interneurons (Saxe et al. 2006; Garthe et al. 2009).”
Fragile X Mental Retardation Protein Regulates Proliferation and Differentiation of Adult Neural Stem/Progenitor Cells (2010, methodology): “Hippocampal neurogenesis has been associated with hippocampus-dependent learning [8,9], and blocking neurogenesis using methods nonexclusive to adult NPCs or new neurons has supported this model [14–17,20].”
The Persistence and Transience of Memory. (2017, background): “For related papers that have examined the relationship between neurogenesis and ﬂexibility, see Burghardt et al. (2012); Garthe et al. (2009), (2016”