Faster is not surer—a comparison of C57BL/6J and 129S2/Sv mouse strains in the watermaze

In recent years the use of genetic manipulations to investigate the molecular mechanisms underlying learning and memory has become a common approach. In a great many cases, the spatial learning ability of mutant mice has been assessed using the Morris watermaze task. The performance of these mice may, however, be strongly influenced by their genetic background and, therefore, the interpretation of their phenotype requires a preliminary characterization of the parental strains. The present study compared 129S2/Sv and C57/BL/6J inbred mouse strains, which have been widely used in deriving lines of genetically modified mice, on the hidden platform version of the watermaze task. During acquisition, the C57 mice displayed shorter escape latencies to find the platform than the 129S2s. Further analysis revealed, however, that the C57 mice also swam faster than the 129S2s. The analysis of path lengths was thus a more reliable measure of spatial learning, and revealed an equal level of performance in the two strains. This conclusion was confirmed during the two probe trials with both strains showing a similar spatial preference for the training site. These results suggest that the 129S2 substrain is no less proficient than the C57 substrain in terms of spatial learning in the watermaze, and also demonstrates the importance of not relying solely on escape latency as a measure of watermaze performance.

[1]  D. Sibley,et al.  Spatial learning deficit in dopamine D(1) receptor knockout mice. , 1999, European journal of pharmacology.

[2]  J. Wehner,et al.  Assessment of learning by the Morris water task and fear conditioning in inbred mouse strains and F1 hybrids: implications of genetic background for single gene mutations and quantitative trait loci analyses , 1997, Neuroscience.

[3]  E. Kandel,et al.  Genetic Demonstration of a Role for PKA in the Late Phase of LTP and in Hippocampus-Based Long-Term Memory , 1997, Cell.

[4]  Alcino J. Silva,et al.  Autophosphorylation at Thr286 of the alpha calcium-calmodulin kinase II in LTP and learning. , 1998, Science.

[5]  David P Wolfer,et al.  Assessing the effects of the 129/Sv genetic background on swimming navigation learning in transgenic mutants: a study using mice with a modified β-amyloid precursor protein gene , 1997, Brain Research.

[6]  Florian Holsboer,et al.  Behavioural performance in three substrains of mouse strain 129 , 1997, Brain Research.

[7]  Alcino J. Silva,et al.  Deficient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein , 1994, Cell.

[8]  D. Ganten,et al.  Sustained Long Term Potentiation and Anxiety in Mice Lacking theMas Protooncogene* , 1998, The Journal of Biological Chemistry.

[9]  S. Tonegawa,et al.  PKCγ mutant mice exhibit mild deficits in spatial and contextual learning , 1993, Cell.

[10]  J. Lübke,et al.  Importance of AMPA receptors for hippocampal synaptic plasticity but not for spatial learning. , 1999, Science.

[11]  K. I. Blum,et al.  Impaired Hippocampal Representation of Space in CA1-Specific NMDAR1 Knockout Mice , 1996, Cell.

[12]  J. Wehner,et al.  Inheritance of spatial learning ability in inbred mice: a classical genetic analysis. , 1989, Behavioral neuroscience.

[13]  J. Rawlins,et al.  Double dissociation of function within the hippocampus: a comparison of dorsal, ventral, and complete hippocampal cytotoxic lesions. , 1999, Behavioral neuroscience.

[14]  J. Rawlins,et al.  A comparison of 129S2/SvHsd and C57BL/6JOlaHsd mice on a test battery assessing sensorimotor, affective and cognitive behaviours: implications for the study of genetically modified mice , 2001, Behavioural Brain Research.

[15]  Paul W. Frankland,et al.  A mouse model for the learning and memory deficits associated with neurofibromatosis type I , 1997, Nature Genetics.

[16]  J. Rawlins,et al.  Dissociating context and space within the hippocampus: effects of complete, dorsal, and ventral excitotoxic hippocampal lesions on conditioned freezing and spatial learning. , 1999, Behavioral neuroscience.

[17]  Jacqueline N. Crawley,et al.  A Proposed Test Battery and Constellations of Specific Behavioral Paradigms to Investigate the Behavioral Phenotypes of Transgenic and Knockout Mice , 1997, Hormones and Behavior.

[18]  A. Beaudet,et al.  Alpha7 nicotinic receptor subunits are not necessary for hippocampal-dependent learning or sensorimotor gating: a behavioral characterization of Acra7-deficient mice. , 1998, Learning & memory.

[19]  R. Gerlai Gene-targeting studies of mammalian behavior: is it the mutation or the background genotype? , 1996, Trends in Neurosciences.

[20]  E. Kandel,et al.  Impaired long-term potentiation, spatial learning, and hippocampal development in fyn mutant mice. , 1992, Science.

[21]  K. I. Blum,et al.  Hippocampal CA1-region-restricted knockout of NMDAR1 gene disrupts synaptic plasticity, place fields, and spatial learning. , 1996, Cold Spring Harbor symposia on quantitative biology.

[22]  Muriel T. Davisson,et al.  Genetic variation among 129 substrains and its importance for targeted mutagenesis in mice , 1997, Nature Genetics.

[23]  Allan Collins,et al.  Behavioral phenotypes of inbred mouse strains: implications and recommendations for molecular studies , 1997, Psychopharmacology.

[24]  T. Bliss,et al.  Normal spatial learning despite regional inhibition of LTP in mice lacking Thy-1 , 1996, Nature.

[25]  S. Tonegawa,et al.  The Essential Role of Hippocampal CA1 NMDA Receptor–Dependent Synaptic Plasticity in Spatial Memory , 1996, Cell.

[26]  Alcino J. Silva,et al.  Deficient hippocampal long-term potentiation in alpha-calcium-calmodulin kinase II mutant mice. , 1992, Science.

[27]  E. Shimizu,et al.  Genetic enhancement of learning and memory in mice , 1999, Nature.

[28]  R. Paylor,et al.  The use of null mutant mice to study complex learning and memory processes , 1996, Behavior genetics.

[29]  R. Morris,et al.  Place navigation impaired in rats with hippocampal lesions , 1982, Nature.

[30]  R. Palmiter,et al.  Disruption of the Metallothionein-III Gene in Mice: Analysis of Brain Zinc, Behavior, and Neuron Vulnerability to Metals, Aging, and Seizures , 1997, The Journal of Neuroscience.

[31]  Alcino J. Silva,et al.  Impaired spatial learning in alpha-calcium-calmodulin kinase II mutant mice. , 1992, Science.