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Cited by 597Neurogenesis and neuroplasticity mechanismsMemory and Neural MechanismsNeuroscience and Neuropharmacology Research

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

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Garthe, Alexander, Behr, Joachim, Kempermann, Gerd·2009·PLoS ONE
DOI 10.1371/journal.pone.0005464PMC PMC2674212
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Abstract

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.

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Authors
Garthe, A., Behr, J., & Kempermann, G.
Affiliations
  • Center for Regenerative Therapies Dresden (DE)
  • Charité – Universitätsmedizin Berlin (DE)
Corresponding author
Kempermann, Gerd
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2009-05-07
Volume
4
Issue
5
Pages
e5464
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0005464
PMC
PMC2674212
OpenAlex
W2001682194
Cited by
597
References
3
Citations by year
2026: 20 · 2025: 17 · 2024: 13 · 2023: 23 · 2022: 31 · 2021: 45 · 2020: 38 · 2019: 24 · 2018: 39 · 2017: 39 · 2016: 40 · 2015: 40 · 2014: 50 · 2013: 49 · 2012: 47
FWCI
13.49
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Deutsche Forschungsgemeinschaft
  • Volkswagen Foundation
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
adult hippocampal neurogenesis, dentate gyrus granule cells, spatial learning, reference memory, reversal learning, temozolomide, long-term potentiation, hippocampal plasticity, search strategies, metric maps, computational models of learning
MeSH terms
Temozolomide, Animals, Behavior, Animal, Dacarbazine, Electrophysiology, Female, Hippocampus, Immunoenzyme Techniques, Mice, Inbred C57BL, Neurons, Psychomotor Performance, Space Perception, Long-Term Potentiation, Maze Learning, Dentate Gyrus, Antineoplastic Agents, Alkylating, Excitatory Postsynaptic Potentials, Mice, Neurogenesis

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