Abstract
Morris water maze (MWM) is widely used to assess cognitive deficits in pre-clinical rodent models. Latency time to reach escape platform is frequently reported, but may be confounded by deficits in visual acuity, or differences in locomotor activity. This study compared performance of Senescence Accelerated Mouse Prone-Strain 8 (SAMP8) and control Senescence Accelerated Mouse Resistant-Strain 1 (SAMR1) mice in classical MWM, relative to performance in a newly developed olfactory-visual maze testing protocol. Performance indicated as the escape time to rescue platform for classical MWM testing showed that SAMP8 mice as young as 6 weeks of age did poorly relative to age-matched SAMR1 mice. The olfactory-visual maze challenge described better discriminated SAMP8 vs. SAMR1 mice than classical MWM testing, based on latency time measures. Consideration of the distance traveled rather than latency time in the classical MWM found no treatment effects between SAMP8 and SAMR1 at 40 weeks of age and the olfactory-visual measures of performance confirmed the classical MWM findings. Longitudinal (repeat) assessment of SAMP8 and SAMR1 performance at 6, 20, 30, and 40 weeks of age in the olfactory-visual testing protocol showed no age-associated deficits in SAMP8 mice to the last age end-point indicated. Collectively, the results from this study suggest the olfactory-visual testing protocol may be advantageous compared to classical MWM as it avoids potential confounders of visual impairment in some strains of mice and indeed, may offer insight into cognitive and behavioral deficits that develop with advanced age in the widely used SAMP8 murine model.
Highlights
The Morris-Water-Maze (MWM) is a widely used visual-spatial learning technique of learning and memory with a strong dependence on hippocampal integrity, synaptic plasticity and NMDA receptor function (Vorhees and Williams, 2006)
The longitudinal design was to consider potential changes in associative memory with aging and we deliberately studied mice preceding substantial frank cognitive deficits that are suggested in SAMP8 mice to develop at greater than ∼50 weeks of age The olfactory-visual cue challenge indicated, was compared to the commonly adopted testing protocol for classic Morris water maze (MWM) protocols, which was to train and test once-only, but in mice of different ages, that being at either 6, 20, 30, or 40 weeks of age
In addition, we show that when performance in classic MWM is assessed once but at different ages, there is no evidence of an age-associated divergence between SAMP8 and SAMR1 control mice up to 40 weeks of age
Summary
The Morris-Water-Maze (MWM) is a widely used visual-spatial learning technique of learning and memory with a strong dependence on hippocampal integrity, synaptic plasticity and NMDA receptor function (Vorhees and Williams, 2006). SAMP8 Performance in Olfactory-Water Maze orientate itself and locate a rescue platform submerged beneath the surface of the water. Prior to performance acquisition measures in MWM, each mouse is repeatedly trained for upto 10 times over several days to learn to find the rescue platform. The rescue platform remains visible and is positioned slightly above the water within a fixed quadrant of the circular pool. Thereafter, for the acquisition phase trialing, the rescue platform is slightly submerged beneath the water within the same quadrant position as during training. Most studies report MWM performance in different groups of animals, at different ages. Few studies report repeated-MWM performance testing in the same group of mice as they age. A longitudinal-study design may be preferable to consider associative memory loss, common in neurodegenerative disorders such as Vascular Dementia and Alzheimer’s disease
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