Hippocampus-dependent Place Learning Enables Spatial Flexibility in C57BL6/N Mice

Overview

Journal Front Behav Neurosci

Specialty Psychology

Date 2013 Jan 8

PMID 23293591

Citations 28

Authors

Karl R Kleinknecht

Benedikt T Bedenk

Sebastian F Kaltwasser

Barbara Grunecker

Yi-Chun Yen

Michael Czisch

Carsten T Wotjak

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Navigating uncertainty: reward location variability induces reorganization of hippocampal spatial representations.

Tessereau C, Xuan F, Mellor J, Dayan P, Dombeck D bioRxiv. 2025; .

PMID: 39829917 PMC: 11741294. DOI: 10.1101/2025.01.06.631465.

Chronic administration of XBD173 ameliorates cognitive deficits and neuropathology via 18 kDa translocator protein (TSPO) in a mouse model of Alzheimer's disease.

Pradhan A, Neumuller T, Klug C, Fuchs S, Schlegel M, Ballmann M Transl Psychiatry. 2023; 13(1):332.

PMID: 37891168 PMC: 10611770. DOI: 10.1038/s41398-023-02630-z.

NCK1 Modulates Neuronal Actin Dynamics and Promotes Dendritic Spine, Synapse, and Memory Formation.

Diab A, Wigerius M, Quinn D, Qi J, Shahin I, Paffile J J Neurosci. 2022; 43(6):885-901.

PMID: 36535770 PMC: 9908320. DOI: 10.1523/JNEUROSCI.0495-21.2022.

Neurobehavioral basis of Maier 3-table and other matching-to-place tasks.

Lalonde R, Strazielle C Cogn Affect Behav Neurosci. 2022; 23(2):237-247.

PMID: 36451026 DOI: 10.3758/s13415-022-01049-1.

Myo-Inositol Levels in the Dorsal Hippocampus Serve as Glial Prognostic Marker of Mild Cognitive Impairment in Mice.

Ebert T, Heinz D, Almeida-Correa S, Cruz R, Dethloff F, Stark T Front Aging Neurosci. 2021; 13:731603.

PMID: 34867270 PMC: 8633395. DOI: 10.3389/fnagi.2021.731603.

References

Liu I, Levy R, Barton J, Iaria G . Age and gender differences in various topographical orientation strategies. Brain Res. 2011; 1410:112-9. DOI: 10.1016/j.brainres.2011.07.005. View

Kamprath K, Wotjak C . Nonassociative learning processes determine expression and extinction of conditioned fear in mice. Learn Mem. 2004; 11(6):770-86. PMC: 534706. DOI: 10.1101/lm.86104. View

Hughey D, KOPPENAAL R . Hippocampal lesions in rats alter learning about intramaze cues. Behav Neurosci. 1987; 101(5):634-43. DOI: 10.1037//0735-7044.101.5.634. View

Etchamendy N, Desmedt A, Cortes-Torrea C, Marighetto A, Jaffard R . Hippocampal lesions and discrimination performance of mice in the radial maze: sparing or impairment depending on the representational demands of the task. Hippocampus. 2003; 13(2):197-211. DOI: 10.1002/hipo.10055. View

Moses S, Sutherland R, McDonald R . Differential involvement of amygdala and hippocampus in responding to novel objects and contexts. Brain Res Bull. 2002; 58(5):517-27. DOI: 10.1016/s0361-9230(02)00820-1. View

Engelmann M, Ebner K, Landgraf R, Wotjak C . Effects of Morris water maze testing on the neuroendocrine stress response and intrahypothalamic release of vasopressin and oxytocin in the rat. Horm Behav. 2006; 50(3):496-501. DOI: 10.1016/j.yhbeh.2006.04.009. View

Mingaud F, Le Moine C, Etchamendy N, Mormede C, Jaffard R, Marighetto A . The hippocampus plays a critical role at encoding discontiguous events for subsequent declarative memory expression in mice. Hippocampus. 2007; 17(4):264-70. DOI: 10.1002/hipo.20262. View

Elliott A, Packard M . Intra-amygdala anxiogenic drug infusion prior to retrieval biases rats towards the use of habit memory. Neurobiol Learn Mem. 2008; 90(4):616-23. DOI: 10.1016/j.nlm.2008.06.012. View

Hartley T, Maguire E, Spiers H, Burgess N . The well-worn route and the path less traveled: distinct neural bases of route following and wayfinding in humans. Neuron. 2003; 37(5):877-88. DOI: 10.1016/s0896-6273(03)00095-3. View

10.

Cabib S, Orsini C, Le Moal M, Piazza P . Abolition and reversal of strain differences in behavioral responses to drugs of abuse after a brief experience. Science. 2000; 289(5478):463-5. DOI: 10.1126/science.289.5478.463. View

11.

McDonald R, Jones J, Richards B, Hong N . A double dissociation of dorsal and ventral hippocampal function on a learning and memory task mediated by the dorso-lateral striatum. Eur J Neurosci. 2006; 24(6):1789-801. DOI: 10.1111/j.1460-9568.2006.05064.x. View

12.

Kassem M, Lagopoulos J, Stait-Gardner T, Price W, Chohan T, Arnold J . Stress-induced grey matter loss determined by MRI is primarily due to loss of dendrites and their synapses. Mol Neurobiol. 2012; 47(2):645-61. DOI: 10.1007/s12035-012-8365-7. View

13.

Grunecker B, Kaltwasser S, Peterse Y, Samann P, Schmidt M, Wotjak C . Fractionated manganese injections: effects on MRI contrast enhancement and physiological measures in C57BL/6 mice. NMR Biomed. 2010; 23(8):913-21. DOI: 10.1002/nbm.1508. View

14.

Packard M . Glutamate infused posttraining into the hippocampus or caudate-putamen differentially strengthens place and response learning. Proc Natl Acad Sci U S A. 1999; 96(22):12881-6. PMC: 23146. DOI: 10.1073/pnas.96.22.12881. View

15.

McDonald R, King A, Hong N . Context-specific interference on reversal learning of a stimulus-response habit. Behav Brain Res. 2001; 121(1-2):149-65. DOI: 10.1016/s0166-4328(01)00160-7. View

16.

Hirsh R . Lack of variability or perseveration: describing the effect of hippocampal ablation. Physiol Behav. 1970; 5(11):1249-54. DOI: 10.1016/0031-9384(70)90035-1. View

17.

Stevens R, Cowey A . Effects of dorsal and ventral hippocampal lesions on spontaneous alternation, learned alternation and probability learning in rats. Brain Res. 1973; 52:203-24. DOI: 10.1016/0006-8993(73)90659-8. View

18.

Etchamendy N, Bohbot V . Spontaneous navigational strategies and performance in the virtual town. Hippocampus. 2007; 17(8):595-9. DOI: 10.1002/hipo.20303. View

19.

Fanselow M, Dong H . Are the dorsal and ventral hippocampus functionally distinct structures?. Neuron. 2010; 65(1):7-19. PMC: 2822727. DOI: 10.1016/j.neuron.2009.11.031. View

20.

Packard M, Wingard J . Amygdala and "emotional" modulation of the relative use of multiple memory systems. Neurobiol Learn Mem. 2004; 82(3):243-52. DOI: 10.1016/j.nlm.2004.06.008. View