Hippocampus-dependent place learning enables spatial flexibility in C57BL6/N mice
Open accessAbstract
Spatial navigation is a fundamental capability necessary in everyday life to locate food, social partners, and shelter. It results from two very different strategies: (1) place learning which enables for flexible way finding and (2) response learning that leads to a more rigid "route following." Despite the importance of knockout techniques that are only available in mice, little is known about mice' flexibility in spatial navigation tasks. Here we demonstrate for C57BL6/N mice in a water-cross maze (WCM) that only place learning enables spatial flexibility and relearning of a platform position, whereas response learning does not. This capability depends on an intact hippocampal formation, since hippocampus lesions by ibotenic acid (IA) disrupted relearning. In vivo manganese-enhanced magnetic resonance imaging revealed a volume loss of ≥60% of the hippocampus as a critical threshold for relearning impairments. In particular the changes in the left ventral hippocampus were indicative of relearning deficits. In summary, our findings establish the importance of hippocampus-dependent place learning for spatial flexibility and provide a first systematic analysis on spatial flexibility in mice.
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Spatial navigation paradigms are known to depend on normal synaptic function in the hippocampal CA1 region.
“spatial navigation paradigms, which are known to be dependent on normal synaptic function in this region (Kleinknecht et al. 2012; Vorhees and Williams 2006).”
From The Serine/Threonine Kinase <scp>NDR2</scp> Regulates Integrin Signaling, Synapse Formation, and Synaptic Plasticity in the Hippocampus (2025) · cites this paper as Kleinknecht et al. 2012
The Introduction describes place learning as a hippocampus-dependent navigation strategy, and the Abstract reports that hippocampal lesions disrupted spatial relearning in C57BL6/N mice. The paper does not establish that spatial navigation paradigms generally depend on normal synaptic function specifically in CA1; its experiment examined hippocampal lesions, not CA1 synaptic function. (LLM, conf=0.86)
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van Heusden, F. C., Bonsón, S. P. I., Stiedl, O., Smit, A. B., & van Kesteren, R. E. (2021) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2021.655449 · Cited by 4 · see citing works
Response and place learning in crayfish spatial behavior
Tierney, A. J., Baker, A., Forward, J., Slight, C., & Yilma, H. (2018) · Learning & Behavior · doi:10.3758/s13420-018-0345-y · Cited by 5 · see citing works
Two-dimensional reward evaluation in mice
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Tessereau, C., Xuan, F., Chen, Z., Mellor, J. R., Dayan, P., & Dombeck, D. A. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.01.06.631465 · Cited by 2 · see citing works
del Ángel, M., Tsutiya, A., Hayani, H., Madencioglu, D., Kul, E., Caliskan, G., Demiray, Y. E., Dityatev, A., & Stork, O. (2025) · Journal of Neurochemistry · doi:10.1111/jnc.70094 · Cited by 1 · see citing works
“To address the implications of decreased connectivity and synaptic plasticity in the hippocampal CA1 area, Ndr2 WT and KO mice were tested in spatial navigation paradigms, which are known to be dependent on normal synaptic function in this region (Kleinknecht et al. 2012; Vorhees and Williams 2006).”
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Motor Asymmetry and the Learning of New Skills by Animals
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Funktionelle Charakterisierung des Two-Pore-Loop-Kanals 2 (TPC2) im endolysosomalen System
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Adult Hippocampal Neurogenesis, Cognitive Flexibility, and Depression
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Neurobehavioral basis of Maier 3-table and other matching-to-place tasks
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- Authors
- Kleinknecht, K. R., Bedenk, B. T., Kaltwasser, S. F., Grünecker, B., Yen, Y.-C., Czisch, M., & Wotjak, C. T.
- Affiliations
- Max Planck Institute of Psychiatry (DE)
- Corresponding author
- Wotjak, Carsten T.
- Venue
- Frontiers in Behavioral Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2012
- Volume
- 6
- Pages
- 87-87
- ISSN
- 1662-5153 (ISSN-L)
- PMC
- PMC3530747
- OpenAlex
- W2088181186
- Cited by
- 46
- References
- 65
- Citations by year
- 2025: 3 · 2023: 1 · 2022: 2 · 2021: 9 · 2020: 1 · 2019: 3 · 2018: 5 · 2017: 4 · 2016: 5 · 2015: 7 · 2014: 4 · 2013: 2
- FWCI
- 2.13
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Behavioral Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- National University of Singapore (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Physical Sciences › Engineering › Automotive Engineering › Spatial Cognition and Navigation
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- hippocampus, place learning, spatial flexibility, spatial navigation, response learning, ibotenic acid lesions, manganese-enhanced MRI, ventral hippocampus, C57BL/6 mice
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