Impaired short- and long-term memory in Ts65Dn mice, a model for Down syndrome

Escorihuela, Rosa M.; Vallina, Iria F.; Martı́nez-Cué, Carmen; Baamonde, Carmela; Dierssen, Mara; Tobeña, Adolf; Flórez, Jesús; Fernández-Teruel, Alberto

doi:10.1016/s0304-3940(98)00317-6

Cited by 153 publications

(112 citation statements)

References 12 publications

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“…On a test of working and reference memory in a water-escape radialarm maze task, learning was impaired in both 4-and 6-month-old Ts65Dn mice . In most other studies, learning and memory deficits in Ts65Dn mice were found at 6 months or older (Demas et al, 1996;Escorihuela et al, 1995Escorihuela et al, , 1998Holtzman et al, 1996;Reeves et al, 1995), although deficits in Ts65Dn mice on some versions of swim tasks are evident as early as 4 months of age (Seo and Isacson, 2005). Thus, the present findings are generally consistent with many reports of memory impairments in this partial trisomy model of Down syndrome, most examining mice at 6 months and older (cf.…”

Section: Spontaneous Alternationsupporting

confidence: 91%

Age-related changes in memory and in acetylcholine functions in the hippocampus in the Ts65Dn mouse, a model of Down syndrome

Chang

Gold

2008

Neurobiology of Learning and Memory

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Spatial working memory and the ability of a cholinesterase inhibitor to enhance memory were assessed at 4, 10, and 16 months of ages in control and Ts65Dn mice, a partial trisomy model of Down syndrome, with possibly significant relationships to Alzheimer's Disease as well. In addition, ACh release during memory testing was measured in samples collected from the hippocampus using in vivo microdialysis at 4, 10, and 22-25 months of age. When tested on a four-arm spontaneous alternation task, the Ts65Dn mice exhibited impaired memory scores at both 4 and 10 months. At 16 months, control performance had declined toward that of the Ts65Dn mice and the difference in scores across genotypes was not significant. Physostigmine (50 μg/kg) fully reversed memory deficits in the Ts65Dn mice in the 4-month-old group but not in older mice. Ts65Dn and control mice exhibited comparable baseline levels of ACh release at all ages tested; these levels did not decline significantly across age in either genotype. ACh release increased significantly during alternation testing only in the young Ts65Dn and control mice. However, the increase in ACh release during alternation testing was significantly greater in control than Ts65Dn mice at this age. The controls exhibited a significant age-related decline in the testing-related increase in ACh release. With only a small increase during testing in young Ts65Dn mice, the age-related decline in responsiveness of ACh release to testing was not significant in these mice. Overall, these results suggest that diminished responsiveness of ACh release in the hippocampus to behavioral testing may contribute memory impairments in Ts65Dn mice.

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Section: Spontaneous Alternationsupporting

confidence: 91%

Age-related changes in memory and in acetylcholine functions in the hippocampus in the Ts65Dn mouse, a model of Down syndrome

Chang

Gold

2008

Neurobiology of Learning and Memory

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“…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). There are, however, significant drawbacks to using the MWM when assaying a molecular phenotype.…”

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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“…Animals were tested in a series of five different paradigms in the Morris water maze consisting of five sessions of place learning for reference memory (days 1-5), one session of removal (day 5), two sessions of reversal (days 6-7), two sessions of cue learning (days 8-9) (Morris, 1984;Escorihuela et al, 1998), and two sets of four sessions of place learning for working memory (days 14-17 and days 21-24) (Whishaw, 1985).…”

Section: Morris Water Maze Testsmentioning

confidence: 99%

Mice lacking the adenosine A₁ receptor have normal spatial learning and plasticity in the CA1 region of the hippocampus, but they habituate more slowly

Giménez-Llort

Masino

Diao

et al. 2005

Synapse

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Using mice with a targeted disruption of the adenosine A 1 receptor (A 1 R), we examined the role of A 1 Rs in hippocampal long-term potentiation (LTP), long-term depression (LTD), and memory formation. Recordings from the Shaffer collateral-CA1 pathway of hippocampal slices from adult mice showed no differences between theta burst and tetanic stimulation-induced LTP in adenosine A 1 receptor knockout (A 1 R −/− ), heterozygote (A 1 R +/− ), and wildtype (A 1 R +/+ ) mice. However, paired pulse facilitation was impaired significantly in A 1 R −/− slices as compared to (A 1 R +/+ ) slices. LTD in the CA1 region was unaffected by the genetic manipulation. The three genotypes showed similar memory acquisition patterns when assessed for spatial reference and working memory in the Morris water maze tasks at 9 months of age. However, 10 months later A 1 R −/− mice showed some deficits in the 6-arm radial tunnel maze test. The latter appeared, however, not due to memory deficits but to decreased habituation to the test environment. Taken together, we observe normal spatial learning and memory and hippocampal CA1 synaptic plasticity in adult adenosine A 1 R knockout mice, but find modifications in arousal-related processes, including habituation, in this knockout model.

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Impaired short- and long-term memory in Ts65Dn mice, a model for Down syndrome

Cited by 153 publications

References 12 publications

Age-related changes in memory and in acetylcholine functions in the hippocampus in the Ts65Dn mouse, a model of Down syndrome

Age-related changes in memory and in acetylcholine functions in the hippocampus in the Ts65Dn mouse, a model of Down syndrome

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

Mice lacking the adenosine A₁ receptor have normal spatial learning and plasticity in the CA1 region of the hippocampus, but they habituate more slowly

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Impaired short- and long-term memory in Ts65Dn mice, a model for Down syndrome

Cited by 153 publications

References 12 publications

Age-related changes in memory and in acetylcholine functions in the hippocampus in the Ts65Dn mouse, a model of Down syndrome

Age-related changes in memory and in acetylcholine functions in the hippocampus in the Ts65Dn mouse, a model of Down syndrome

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

Mice lacking the adenosine A1 receptor have normal spatial learning and plasticity in the CA1 region of the hippocampus, but they habituate more slowly

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Mice lacking the adenosine A₁ receptor have normal spatial learning and plasticity in the CA1 region of the hippocampus, but they habituate more slowly