The Barnes Maze Task Reveals Specific Impairment of Spatial Learning Strategy in the Intrahippocampal Kainic Acid Model for Temporal Lobe Epilepsy
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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.
KeywordsThe Barnes maze Temporal lobe epilepsy Intrahippocampal post-status epilepticus Kainic Acid model Spatial learning and memory Search strategy
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.
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.
- 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
- 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
- 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
- 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.Paxinos G, Franklin KBJ (2001) The mouse brain in stereotaxic coordinates 2. Academic Press, San DiegoGoogle Scholar
- 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
- 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
- 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