Multidisciplinary approaches for investigating the mechanisms of hippocampus-dependent memory: a focus on inbred mouse strains

Schimanski, Lesley A.; Nguyen, Peter V.

doi:10.1016/j.neubiorev.2004.04.002

Cited by 58 publications

(50 citation statements)

References 188 publications

(194 reference statements)

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“…The hidden version of the MWM is an attractive behavioral test because it couples spatial learning (mice are required to use spatial cues from the environment to learn the location of the platform) which is considered to be a hippocampal measure, with a stressful situation (because the mice find water aversive) (Schimanski and Nguyen 2004). For Down syndromerelated studies, it has the added attraction of being the most commonly used test, providing a robust phenotype in many mouse models (Escorihuela et al 1998;Sago et al 1998;Chabert et al 2004;Martinez-Cue et al 2005;Ahn et al 2006).…”

Section: Discussionmentioning

confidence: 99%

Editing of the serotonin 2C receptor pre-mRNA: Effects of the Morris Water Maze

Stasko

Costa

et al. 2007

Gene

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The pre-mRNA encoding the serotonin 2C receptor, HTR2C (official mouse gene symbol, Htr2c), is subject to adenosine deamination that produces inosine at five sites within the coding region. Combinations of this site-specific A-to-I editing can produce 32 different mRNA sequences encoding 24 different protein isoforms with differing biochemical and pharmacological properties. Studies in humans have reported abnormalities in patterns of HTR2C editing in psychiatric disorders, and studies in rodents show altered patterns of editing in response to drug treatments and stressful situations. To further explore the biological significance of editing of the Htr2c mRNA and its regulation, we have examined patterns of Htr2c editing in C57BL/6J mice after exposure to the hidden platform version of the Morris Water Maze, a test of spatial learning that, in mice, is also associated with stress. In brains of both swimming controls and mice trained to find the platform, subtle time dependent changes in editing patterns are seen as soon as one hour after a probe trial and typically last less than 24 hours. Changes in whole brain with cerebellum removed differ from those seen in isolated hippocampus and cortex. Unexpectedly, in hippocampi from subsets of mice, abnormally low levels of editing were seen that were not correlated with behavior or with editing levels in cortex. These data implicate responses to spatial learning and stress, in addition to stochastic processes, in the generation of subtle changes in editing patterns of Htr2c.

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Section: Discussionmentioning

confidence: 99%

Editing of the serotonin 2C receptor pre-mRNA: Effects of the Morris Water Maze

Stasko

Costa

et al. 2007

Gene

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“…By the F13 generation, the behavioral performance in the wild-type mice closely resembled that of C57BL/6 mice (after 13 backcrosses, 90 -95% of the genes are homozygous and of C57BL/6 origin), in contrast to wild-type mice from the F2 generation, which more resembled CBA mice. It is well established that C57BL/6 mice perform better in the water maze than CBA mice (Schimanski and Nguyen, 2004), and therefore the original water maze deficit may have reflected a higher degree of CBA character in the background genes selected specifically with the knock-out mice. In contrast, by the time of the present study, the mice were on a more pure C57BL/6 background, and hence there were no differences between wild-type and mutant mice in the water maze.…”

Section: Discrimination Ratiomentioning

confidence: 99%

NMDA Receptor Subunit NR2A Is Required for Rapidly Acquired Spatial Working Memory But Not Incremental Spatial Reference Memory

Bannerman¹,

Niewoehner²,

Lyon³

et al. 2008

J. Neurosci.

176

120

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NMDA receptors (NMDARs) containing NR2A (1) subunits are key contributors to hippocampal long-term potentiation (LTP) induction in adult animals and have therefore been widely implicated in hippocampus-dependent spatial learning. Here we show that mice lacking the NR2A subunit or its C-terminal intracellular domain exhibit impaired spatial working memory (SWM) but normal spatial reference memory (SRM). Both NR2A mutants acquired the SRM version of the water maze task, and the SRM component of the radial maze, as well as controls. They were, however, impaired on a non-matching-to-place T-maze task, and on the SWM component of the radial maze. In addition, NR2A knock-out mice displayed a diminished spatial novelty preference in a spontaneous exploration Y-maze task, and were impaired on a T-maze task in which distinctive inserts present on the floor of the maze determined which goal arm contained the reward, but only if there was a discontiguity between the conditional cue and the place at which the reward was delivered. This dissociation of spatial memory into distinctive components is strikingly similar to results obtained with mice lacking glutamate receptor-A (GluR-A)-containing AMPA receptors, which support long-term potentiation expression. These results identify a specific role for a NMDAR-dependent signaling pathway that leads to the activation of a GluR-A-dependent expression mechanism in a rapidly acquired, flexible form of spatial memory. This mechanism depends on the C-terminal intracellular domain of the NR2A subunit. In contrast, the ability to associate a particular spatial location with the water maze escape platform or food reward is NR2A independent, as well as GluR-A independent.

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“…These data underscore the notion that it is difficult to make broadly based, generic correlations between fear conditioning (a key memory task used in mouse behavioural research) (see Crawley, 2000;Schimanski and Nguyen, 2004) and LTP. Some consistent correlations exist (Table·1), but not every strain tested has yielded data that would definitively establish generic correlations between particular forms of LTP and fear conditioning.…”

Section: Hippocampal Synaptic Plasticity and Memory Functionmentioning

confidence: 66%

“…Other inbred mouse strains also display deficits in particular forms of LTP in hippocampal and amygdalar circuits, as assessed using in vitro techniques (Schimanski and Nguyen, 2004;Schimanski and Nguyen, 2005a;Schimanski and Nguyen, 2005b). It should be noted that many studies using genetic methods have reached similar conclusions, and that inducible systems, e.g.…”

Section: Strain-related Variations In Hippocampal Ltp and Ltdmentioning

confidence: 97%

“…Brief coverage of memory function is provided to underscore the notion that some types of behavioural memory can be correlated with particular forms of synaptic plasticity in inbred strains. Readers seeking more in-depth coverage of memory functions in mice, and quantitative genetics of mouse behaviour, should consult additional sources (Crawley, 2000;Wehner et al, 2001;Wahlsten et al, 2003;Greenspan, 2004;Schimanski and Nguyen, 2004).…”

Section: Introductionmentioning

confidence: 99%

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Comparative plasticity of brain synapses in inbred mouse strains

Nguyen

2006

Journal of Experimental Biology

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SUMMARY One niche of experimental biology that has experienced considerable progress is the neurobiology of learning and memory. A key contributor to such progress has been the widespread use of transgenic and `knockout' mice to elucidate the mechanisms of identifiable phenotypes of learning and memory. Inbred mouse strains are needed to generate genetically modified mice. However, genetic variations between inbred strains can confound the interpretation of cellular neurophysiological phenotypes of mutant mice. It is known that altered physiological strength of synaptic transmission (`synaptic plasticity') can modify and regulate learning and memory. Characterization of the synaptic phenotypes of inbred mouse strains is needed to identify the most appropriate strains to use for generating mutant mouse models of memory function. More importantly, comparative electrophysiological analyses of inbred mice per se can also shed light on which forms of synaptic plasticity underlie particular types of learning and memory. Many such analyses have focused on synaptic plasticity in the hippocampus because of the critical roles of this brain structure in the formation and consolidation of long-term memories. Comparative electrophysiological data obtained from several inbred mouse strains are reviewed here to highlight the following key notions: (1) synaptic plasticity is influenced by the genetic backgrounds of inbred mice; (2) the plasticity of hippocampal synapses in inbred mice is`tuned' to particular temporal patterns of activity; (3) long-term potentiation, but not long-term depression, is a cellular correlate of behavioural memory performance in some strains; (4) synaptic phenotyping of inbred mouse strains can identify cellular models of memory impairment that can be used to elucidate mechanisms that may cause specific memory deficits.

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Multidisciplinary approaches for investigating the mechanisms of hippocampus-dependent memory: a focus on inbred mouse strains

Cited by 58 publications

References 188 publications

Editing of the serotonin 2C receptor pre-mRNA: Effects of the Morris Water Maze

Editing of the serotonin 2C receptor pre-mRNA: Effects of the Morris Water Maze

NMDA Receptor Subunit NR2A Is Required for Rapidly Acquired Spatial Working Memory But Not Incremental Spatial Reference Memory

Comparative plasticity of brain synapses in inbred mouse strains

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