Barnes maze, a useful task to assess spatial reference memory in the mice

Sunyer, Berta; Patil, Sudarshan; Höger, Harald; Lübec, Gert

doi:10.1038/nprot.2007.390

Cited by 145 publications

(143 citation statements)

References 19 publications

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“…The Barnes Maze was performed as previously described (43). Animals were trained with two trials each day for 10 d, with an intertrial interval of 1 h. After training, animals were tested via probe trial 7 d later.…”

Section: Methodsmentioning

confidence: 99%

Inositol polyphosphate multikinase is a transcriptional coactivator required for immediate early gene induction

Paul

Smith

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Profound induction of immediate early genes (IEGs) by neural activation is a critical determinant for plasticity in the brain, but intervening molecular signals are not well characterized. We demonstrate that inositol polyphosphate multikinase (IPMK) acts noncatalytically as a transcriptional coactivator to mediate induction of numerous IEGs. IEG induction by electroconvulsive stimulation is virtually abolished in the brains of IPMK-deleted mice, which also display deficits in spatial memory. Neural activity stimulates binding of IPMK to the histone acetyltransferase CBP and enhances its recruitment to IEG promoters. Interestingly, IPMK regulation of CBP recruitment and IEG induction does not require its catalytic activities. Dominant-negative constructs, which prevent IPMK-CBP binding, substantially decrease IEG induction. As IPMK is ubiquitously expressed, its epigenetic regulation of IEGs may influence diverse nonneural and neural biologic processes.inositol phosphates | learning

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Section: Methodsmentioning

confidence: 99%

Inositol polyphosphate multikinase is a transcriptional coactivator required for immediate early gene induction

Paul

Smith

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…Mice were immunized to induce EAE and treated daily with either vehicle or 2-PMPA for ∼4 wk and subjected to Barnes maze testing as previously described (57). Paths were recorded and latency to the target hole, path efficiency, speed, and directional times were calculated using ANY-maze software (Stoelting).…”

Section: Methodsmentioning

confidence: 99%

Inhibition of Glutamate Carboxypeptidase II (GCPII) activity as a treatment for cognitive impairment in multiple sclerosis

Rahn

Watkins

Alt³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Half of all patients with multiple sclerosis (MS) experience cognitive impairment, for which there is no pharmacological treatment. Using magnetic resonance spectroscopy (MRS), we examined metabolic changes in the hippocampi of MS patients, compared the findings to performance on a neurocognitive test battery, and found that N-acetylaspartylglutamate (NAAG) concentration correlated with cognitive functioning. Specifically, MS patients with cognitive impairment had low hippocampal NAAG levels, whereas those with normal cognition demonstrated higher levels. We then evaluated glutamate carboxypeptidase II (GCPII) inhibitors, known to increase brain NAAG levels, on cognition in the experimental autoimmune encephalomyelitis (EAE) model of MS. Whereas GCPII inhibitor administration did not affect physical disabilities, it increased brain NAAG levels and dramatically improved learning and memory test performance compared with vehicle-treated EAE mice. These data suggest that NAAG is a unique biomarker for cognitive function in MS and that inhibition of GCPII might be a unique therapeutic strategy for recovery of cognitive function.G lutamate carboxypeptidase II (GCPII), previously called Nacetylated-α-linked acidic dipeptidase (NAALADase), is a membrane-bound enzyme expressed on the surface of astrocytes that catalyzes the cleavage of N-acetylaspartylglutamate (NAAG) into N-acetylaspartate (NAA) and glutamate ( Fig. 1) (1, 2). NAAG, the most abundant neuropeptide in the mammalian brain, is a selective agonist for metabotropic glutamate receptor 3 (mGluR3) (1, 2). mGluR3s are expressed on the surface of presynaptic neurons and astrocytes in the CNS. Activation of mGluR3s by NAAG reduces cAMP and cGMP levels, inhibits glutamate release, and stimulates a release of transforming growth factor beta (1, 2). A recent study reported impaired performance on spatial reference and working memory tasks in mGluR2/3 knockout mice (3), suggesting a role for group II mGluRs in cognitive function.Cognitive impairment is a frequent comorbidity of many neurological diseases, including multiple sclerosis (MS). MS affects over 2 million individuals worldwide, and ∼40-65% of all MS patients experience cognitive impairment (4). The most commonly and severely affected facets of cognition in MS patients are anterograde episodic memory, working memory, and processing speed (5-7), and these impairments strongly contribute to the high frequency of unemployment in MS patient populations (8). Global brain atrophy, candidate genetic risk factors, accelerated inflammatory processes (7), and dysregulated signaling pathways (9) have been implicated as contributing factors, but an incomplete understanding of the molecular mechanisms behind cognitive impairment in MS has prevented the development and Food and Drug Administration (FDA) approval of drug therapies.The most widely used animal model of MS, experimental autoimmune encephalomyelitis (EAE), is a valuable tool for developing treatments for MS. Three FDA-approved disease-modifying agents were deve...

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“…Previous spatial memory studies in squamates have been criticized on methodological issues. Thus, we used the Barnes maze, a standard apparatus and methodology used to test spatial memory in many taxa [9]. The Barnes maze was a circular platform (73.66 cm high, 105.74 cm diameter) with 10 holes, equidistant from each other (26.04 cm); each hole was 15.54 cm from the edge of the maze.…”

Section: Methodsmentioning

confidence: 99%

Spatial memory: are lizards really deficient?

et al. 2012

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In many animals, behaviours such as territoriality, mate guarding, navigation and food acquisition rely heavily on spatial memory abilities; this has been demonstrated in diverse taxa, from invertebrates to mammals. However, spatial memory ability in squamate reptiles has been seen as possible, at best, or non-existent, at worst. Of the few previous studies testing for spatial memory in squamates, some have found no evidence of spatial memory while two studies have found evidence of spatial memory in snakes, but have been criticized based on methodological issues. We used the Barnes maze, a common paradigm to test spatial memory abilities in mammals, to test for spatial memory abilities in the side-blotched lizard ( Uta stansburiana ). We found the existence of spatial memory in this species using this spatial task. Thus, our study supports the existence of spatial memory in this squamate reptile species and seeks to parsimoniously align this species with the diverse taxa that demonstrate spatial memory ability.

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Barnes maze, a useful task to assess spatial reference memory in the mice

Cited by 145 publications

References 19 publications

Inositol polyphosphate multikinase is a transcriptional coactivator required for immediate early gene induction

Inositol polyphosphate multikinase is a transcriptional coactivator required for immediate early gene induction

Inhibition of Glutamate Carboxypeptidase II (GCPII) activity as a treatment for cognitive impairment in multiple sclerosis

Spatial memory: are lizards really deficient?

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