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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
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
Helmstaedter C, Elger CE (2009) Chronic temporal lobe epilepsy: a neurodevelopmental or progressively dementing disease? Brain. https://doi.org/10.1093/brain/awp182
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
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):4499–4509
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
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
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
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
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
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
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
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
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
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
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
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
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
Paxinos G, Franklin KBJ (2001) The mouse brain in stereotaxic coordinates 2. Academic Press, San Diego
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
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
Rosenfeld CS, Ferguson SA (2014) Barnes maze testing strategies with small and large rodent models. J Vis Exp. https://doi.org/10.3791/51194
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
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
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
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
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
Vorhees CV, Williams MT (2014) Assessing spatial learning and memory in rodents. Inst Lab Anim Res J. https://doi.org/10.1093/ilar/ilu013
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
Bell BD (2013) Route learning impairment in temporal lobe epilepsy. Epilepsy Behav. https://doi.org/10.1016/j.yebeh.2012.07.023
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
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
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.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
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.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Van Den Herrewegen, Y., Denewet, L., Buckinx, A. et al. The Barnes Maze Task Reveals Specific Impairment of Spatial Learning Strategy in the Intrahippocampal Kainic Acid Model for Temporal Lobe Epilepsy. Neurochem Res 44, 600–608 (2019). https://doi.org/10.1007/s11064-018-2610-z
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11064-018-2610-z