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The Barnes Maze Task Reveals Specific Impairment of Spatial Learning Strategy in the Intrahippocampal Kainic Acid Model for Temporal Lobe Epilepsy

  • Yana Van Den Herrewegen
  • Lissa Denewet
  • An Buckinx
  • Giulia Albertini
  • Ann Van Eeckhaut
  • Ilse Smolders
  • Dimitri De Bundel
Original Paper
  • 114 Downloads

Abstract

Temporal lobe epilepsy (TLE) is an acquired form of focal epilepsy, in which patients not only suffer from unprovoked, devastating seizures, but also from severe comorbidities, such as cognitive dysfunction. Correspondingly, several animal models of TLE exhibit memory dysfunction, especially spatial memory. The Morris water maze test is the most commonly used test for assessing spatial learning and memory in rodents. However, high stress and poor swimming abilities are common confounders and may contribute to misinterpretation. Particularly epileptic mice show altered behaviour during the test as they fail to understand the paradigm context. In the Barnes maze test, a dry-land maze test for spatial learning and memory that uses milder aversive stimuli, these drawbacks have not yet been reported. In the present study, we use this task to evaluate spatial learning and memory in the intrahippocampal kainic acid mouse model of TLE. We demonstrate that the epileptic mice understand the Barnes maze paradigm context, as they learn the location of the escape-chamber by using a serial search strategy but fail to develop the more efficient spatial search strategy. Our data indicate that the Barnes maze may be a better alternative to the Morris water maze for assessing search strategies and impairment of learning and memory in epileptic mice.

Keywords

The Barnes maze Temporal lobe epilepsy Intrahippocampal post-status epilepticus Kainic Acid model Spatial learning and memory Search strategy 

Notes

Acknowledgements

Yana Van Den Herrewegen is a research fellow of the Fund for Scientific Research Flanders (FWO). An Buckinx is a research fellow of the Fund for Strategic Basic Research (SB-FWO). We would like to thank Gino De Smet for his technical assistance. This study was supported by the Scientific Fund Willy Gepts of UZ Brussel, the Queen Elizabeth Medical Foundation (ING prize) and the Vrije Universiteit Brussel.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical Approval

All procedures were carried out in accordance with the National Rules on Animal Experimentation and were approved by the Ethical Committee for Animal Experiments of the Faculty of Medicine and Pharmacy of the Vrije Universiteit Brussel, Brussels, Belgium.

Research Involving Human Participants

This article does not contain any studies with human participants.

Supplementary material

11064_2018_2610_MOESM1_ESM.pdf (211 kb)
Supplementary material 1 (PDF 210 KB)

References

  1. 1.
    Panayiotopoulos CP (2006) Temporal lobe epilepsy (TLE). Medicinae. https://www.epilepsy.com/learn/professionals/about-epilepsy-seizures/symptomatic-and-probably-symptomatic-focal-epilepsies-0. Accessed 11 April 2018
  2. 2.
    Helmstaedter C, Elger CE (2009) Chronic temporal lobe epilepsy: a neurodevelopmental or progressively dementing disease? Brain.  https://doi.org/10.1093/brain/awp182 PubMedGoogle Scholar
  3. 3.
    Miltiadous P, Stamatakis A, Koutsoudaki PN, Tiniakos DG, Stylianopoulou F (2011) IGF-I ameliorates hippocampal neurodegeneration and protects against cognitive deficits in an animal model of temporal lobe epilepsy. Exp Neurol 231(2):223–235.  https://doi.org/10.1016/j.expneurol.2011.06.014 CrossRefPubMedGoogle Scholar
  4. 4.
    Han T, Qin Y, Mou C, Wang M, Jiang M, Liu B (2016) Seizure induced synaptic plasticity alteration in hippocampus is mediated by IL-1β receptor through PI3K/Akt pathway. Am J Transl Res 8(10):4499–4509PubMedPubMedCentralGoogle Scholar
  5. 5.
    Shapiro LA, Wang L, Ribak CE (2008) Rapid astrocyte and microglial activation following pilocarpine-induced seizures in rats. Epilepsia.  https://doi.org/10.1111/j.1528-1167.2008.01491.x Google Scholar
  6. 6.
    Gröticke I, Hoffmann K, Löscher W (2008) Behavioral alterations in a mouse model of temporal lobe epilepsy induced by intrahippocampal injection of kainate. Exp Neurol.  https://doi.org/10.1016/j.expneurol.2008.04.036 Google Scholar
  7. 7.
    Liu Z, Gatt A, Werner SJ, Mikati MA, Holmes GL (1994) Long-term behavioral deficits following pilocarpine seizures in immature rats. Epilepsy Res.  https://doi.org/10.1016/0920-1211(94)90062-0 Google Scholar
  8. 8.
    Gröticke I, Hoffmann K, Löscher W (2007) Behavioral alterations in the pilocarpine model of temporal lobe epilepsy in mice. Exp Neurol.  https://doi.org/10.1016/j.expneurol.2007.06.021 Google Scholar
  9. 9.
    Inostroza M, Cid E, Brotons-Mas J, Gal B, Aivar P, Uzcategui YG, Sandi C, Menendez de la Prida L (2011) Hippocampal-dependent spatial memory in the water maze is preserved in an experimental model of temporal lobe epilepsy in rats. PLoS ONE.  https://doi.org/10.1371/journal.pone.0022372 PubMedPubMedCentralGoogle Scholar
  10. 10.
    Müller CJ, Gröticke I, Bankstahl M, Löscher W (2009) Behavioral and cognitive alterations, spontaneous seizures, and neuropathology developing after a pilocarpine-induced status epilepticus in C57BL/6 mice. Exp Neurol.  https://doi.org/10.1016/j.expneurol.2009.05.035 Google Scholar
  11. 11.
    Murphy GG (2013) Spatial learning and memory—what’s TLE got to do with it? Epilepsy Curr.  https://doi.org/10.5698/1535-7511-13.1.26 PubMedPubMedCentralGoogle Scholar
  12. 12.
    Harrison FE, Hosseini AH, McDonald MP (2009) Endogenous anxiety and stress responses in water maze and Barnes maze spatial memory tasks. Behav Brain Res.  https://doi.org/10.1016/j.bbr.2008.10.015 PubMedCentralGoogle Scholar
  13. 13.
    Hölscher C (1999) Stress impairs performance in spatial water maze learning tasks. Behav Brain Res.  https://doi.org/10.1016/S0166-4328(98)00134-X PubMedGoogle Scholar
  14. 14.
    Barnes CA (1979) Memory deficits associated with senescence: a neurophysiological and behavioral study in the rat. J Comp Physiol Psychol.  https://doi.org/10.1037/h0077579 PubMedGoogle Scholar
  15. 15.
    Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG (2010) Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biol.  https://doi.org/10.1371/journal.pbio.1000412 PubMedPubMedCentralGoogle Scholar
  16. 16.
    Riban V, Bouilleret V, Pham-Lê BT, Fritschy JM, Marescaux C, Depaulis A (2002) Evolution of hippocampal epileptic activity during the development of hippocampal sclerosis in a mouse model of temporal lobe epilepsy. Neuroscience.  https://doi.org/10.1016/S0306-4522(02)00064-7 PubMedGoogle Scholar
  17. 17.
    Duveau V, Pouyatos B, Bressand K, Bouyssières C, Chabrol T, Roche Y, Depaulis A, Roucard C (2016) Differential effects of antiepileptic drugs on focal seizures in the intrahippocampal kainate mouse model of mesial temporal lobe epilepsy. CNS Neurosci Ther.  https://doi.org/10.1111/cns.12523 PubMedGoogle Scholar
  18. 18.
    Paxinos G, Franklin KBJ (2001) The mouse brain in stereotaxic coordinates 2. Academic Press, San DiegoGoogle Scholar
  19. 19.
    Sunyer B, Patil S, Höger H, Lubec G (2007) Barnes maze, a useful task to assess spatial reference memory in the mice. Protoc Exch.  https://doi.org/10.1038/nprot.2007.390 Google Scholar
  20. 20.
    Harrison FE, Reiserer RS, Tomarken AJ, McDonald MP (2006) Spatial and nonspatial escape strategies in the Barnes maze. Learn Mem. http://www.learnmem.org/cgi/doi/10.1101/lm.334306
  21. 21.
    Rosenfeld CS, Ferguson SA (2014) Barnes maze testing strategies with small and large rodent models. J Vis Exp.  https://doi.org/10.3791/51194 PubMedPubMedCentralGoogle Scholar
  22. 22.
    Bach ME, Hawkins RD, Osman M, Kandel ER, Mayford M (1995) Impairment of spatial but not contextual memory in CaMKII mutant mice with a selective loss of hippocampal LTP in the range of the theta frequency. Cell.  https://doi.org/10.1016/0092-8674(95)90010-1 PubMedGoogle Scholar
  23. 23.
    Heinrich C, Nitta N, Flubacher A, Müller M, Fahrner A, Kirsch M, Freiman T, Suzuki F, Depaulis A, Frotscher M, Haas CA (2006) Reelin deficiency and displacement of mature neurons, but not neurogenesis, underlie the formation of granule cell dispersion in the epileptic hippocampus. J Neurosci.  https://doi.org/10.1523/JNEUROSCI.5516-05.2006 PubMedGoogle Scholar
  24. 24.
    Klein S, Bankstahl JP, Löscher W, Bankstahl M (2015) Sucrose consumption test reveals pharmacoresistant depression-associated behavior in two mouse models of temporal lobe epilepsy. Exp Neurol.  https://doi.org/10.1016/j.expneurol.2014.09.004 PubMedGoogle Scholar
  25. 25.
    Pearson JN, Schulz KM, Patel M (2014) Specific alterations in the performance of learning and memory tasks in models of chemoconvulsant-induced status epilepticus. Epilepsy Res.  https://doi.org/10.1016/j.eplepsyres.2014.04.003 PubMedPubMedCentralGoogle Scholar
  26. 26.
    McKee HR, Privitera MD (2017) Stress as a seizure precipitant: identification, associated factors, and treatment options. Seizure.  https://doi.org/10.1016/j.seizure.2016.12.009 PubMedGoogle Scholar
  27. 27.
    Vorhees CV, Williams MT (2014) Assessing spatial learning and memory in rodents. Inst Lab Anim Res J.  https://doi.org/10.1093/ilar/ilu013 Google Scholar
  28. 28.
    Cánovas R, León I, Serrano P, Roldán MD, Cimadevilla JM (2011) Spatial navigation impairment in patients with refractory temporal lobe epilepsy: evidence from a new virtual reality-based task. Epilepsy Behav.  https://doi.org/10.1016/j.yebeh.2011.07.021 PubMedGoogle Scholar
  29. 29.
    Bell BD (2013) Route learning impairment in temporal lobe epilepsy. Epilepsy Behav.  https://doi.org/10.1016/j.yebeh.2012.07.023 Google Scholar
  30. 30.
    Oliveira CV, Grigoletto J, Funck VR, Ribeiro LR, Freire Royes LF, Fighera MR, Furian AF, Oliveira MS (2015) Evaluation of potential gender-related differences in behavioral and cognitive alterations following pilocarpine-induced status epilepticus in C57BL/6 mice. Physiol Behav.  https://doi.org/10.1016/j.physbeh.2015.03.004 Google Scholar
  31. 31.
    Illouz T, Madar R, Clague C, Griffioen KJ, Louzoun Y, Okun E (2016) Unbiased classification of spatial strategies in the Barnes maze. Bioinformatics.  https://doi.org/10.1093/bioinformatics/btw376 PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information, Research Group Experimental Pharmacology, Center for Neurosciences (C4N)Vrije Universiteit Brussel (VUB)BrusselsBelgium

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