The testing of cognitive enhancers could benefit from the development of novel behavioural tasks that display better translational relevance for daily memory and permit the examination of potential targets in a within-subjects manner with less variability. We here outline an optimized spatial 'everyday memory' task. We calibrate it systematically by interrogating certain well-established determinants of memory and consider its potential for revealing novel features of encoding-related gene activation. Rats were trained in an event arena in which food was hidden in sandwells in a different location everyday. They found the food during an initial memory-encoding trial and were then required to remember the location in six alternative choice or probe trials at various time-points later. Training continued daily over a period of 4 months, realizing a stable high level of performance and characterized by delay-dependent forgetting over 24 h. Spaced but not massed access to multiple rewards enhanced the persistence of memory, as did post-encoding administration of the PDE4 inhibitor Rolipram. Quantitative PCR and then genome-wide analysis of gene expression led to a new observation - stronger gene-activation in hippocampus and retrosplenial cortex following spaced than massed training. In a subsidiary study, a separate group of animals replicated aspects of this training profile, going on to show enhanced memory when training was subject to post-encoding environmental novelty. Distinctive features of this protocol include its potential validity as a model of memory encoding used routinely by human subjects everyday, and the possibility of multiple within-subject comparisons to speed up assays of novel compounds.
Keywords: RNAseq; event arena; gene expression; learning; spaced training.
© 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.