Where to place the rewards? Exploration bias in mice influences performance in the classic hole-board spatial memory test
The classic hole-board paradigm (a square arena with 16 holes arranged equidistantly in a 4 × 4 pattern) assesses both exploration and spatial memory in rodents. For spatial memory training, food rewards are hidden in a fixed set of holes. The animal must not visit (i.e. nose-poke) the holes that are never baited (reference memory; RM) nor re-visit a baited hole within a session (working memory; WM). However, previous exploratory bias may affect performance during reward searching. During habituation sessions with either all holes rewarded or all holes empty, mice intrinsically preferred poking peripheral holes (especially those located in the maze’s corners) over centre holes. During spatial memory training, mice progressively shifted their hole pokes and staying time to the central area that contained hidden rewards, while mice exposed to the empty apparatus still preferred the periphery. A group of pseudotrained mice, for whom rewards were located randomly throughout the maze, also increased their central preference. Furthermore, reward location influenced memory measures. Most repeated pokes (WM-errors) were scored in the locations that were most intrinsically appealing to mice (i.e. the corner and wall-baited holes), supporting a strong influence of previous exploratory bias. Regarding RM, finding rewards located in the centre holes, which were initially less preferred, entailed more difficulty and required more trials to learn. This outcome was confirmed by a second experiment that varied the pattern of rewarded holes, as well as the starting positions. Therefore, reward location is a relevant aspect to consider when designing a hole-board memory task.
KeywordsHabituation Periphery Anxiety Corner Reference memory Working memory
This study was funded by grants from the Spanish Ministry of Economy and Competitiveness (MINECO, Agencia Estatal de Investigación) cofounded by the European Research Development Fund -AEI/FEDER, UE- (PSI2015-73156-JIN to E.C.O.; PSI2017-82604R to L.J.S.) and from University of Malaga (Plan Propio 2017—‘Ayudas para proyectos dirigidos por jóvenes investigadores’, PPIT.UMA.B1.2017/38 to P.S.P). Author P.S.P. holds a ‘Juan de la Cierva-formación’ grant from the Spanish Ministry of Economy, Industry and Competitiveness (code: FJCI-2015-23925). Author M.M.P. holds Predoctoral contract from University of Malaga (Plan Propio 2017). Author F.A.G holds Young researchers contract from the University of Malaga co-funded by the Regional Government of Andalusia and the European Social Fund. Author E.C.O holds a ‘Jóvenes Investigadores’ grant (code: PSI2015-73156-JIN) from MINECO-AEI/FEDER, UE. The authors acknowledge CIBERTEC for their technical assistance with the automatised hole-board apparatus and the IBIMA’s common support structures of Animal Experimentation (Animal Facility at the University of Málaga) for the maintenance of mice, and of Methodological and Statistical Consulting for their statistical advice.
Compliance with ethical standards
Conflict of interest
The authors do not have any conflicts of interest.
- Castilla-Ortega E, Sanchez-Lopez J, Hoyo-Becerra C, Matas-Rico E, Zambrana-Infantes E, Chun J, De Fonseca FR, Pedraza C, Estivill-Torrus G, Santin LJ (2010) Exploratory, anxiety and spatial memory impairments are dissociated in mice lacking the LPA1 receptor. Neurobiol Learn Mem 94:73–82. https://doi.org/10.1016/j.nlm.2010.04.003 CrossRefGoogle Scholar
- Clark BJ, Hamilton DA, Whishaw IQ (2006) Motor activity (exploration) and formation of home bases in mice (C57BL/6) influenced by visual and tactile cues: modification of movement distribution, distance, location, and speed. Physiol Behav 87:805–816 https://doi.org/10.1016/j.physbeh.2006.01.026 CrossRefGoogle Scholar
- Sampedro-Piquero P, Moreno-Fernandez RD, Mañas-Padilla MC, Gil-Rodriguez S, Gavito AL, Pavon FJ, Pedraza C, Garcia-Fernandez M, Ladron de Guevara-Miranda D, Santin LJ, Castilla-Ortega E (2018) Training memory without aversion: appetitive hole-board spatial learning increases adult hippocampal neurogenesis. Neurobiol Learn Mem 151:35–42. https://doi.org/10.1016/j.nlm.2018.03.023 CrossRefGoogle Scholar
- van der Staay FJ, Gieling ET, Pinzon NE, Nordquist RE, Ohl F (2012) The appetitively motivated “cognitive” holeboard: a family of complex spatial discrimination tasks for assessing learning and memory. Neurosci Biobehav Rev 36:379–403. https://doi.org/10.1016/j.neubiorev.2011.07.008 CrossRefGoogle Scholar
- Winne J, Teixeira L, de Andrade Pessoa J, Gavioli EC, Soares-Rachetti V, Andre E, Lobao-Soares B (2015) There is more to the picture than meets the rat: a study on rodent geometric shape and proportion preferences. Behav Brain Res 284:187–195. https://doi.org/10.1016/j.bbr.2015.02.018 CrossRefGoogle Scholar
- Woldeit ML, Korz V (2010) Theta oscillations during holeboard training in rats: different learning strategies entail different context-dependent modulations in the hippocampus. Neuroscience 165:642–653. https://doi.org/10.1016/j.neuroscience.2009.11.002 CrossRefGoogle Scholar