Spatial Working Memory In Mice Research Articles

P1-010: Native Aβ-oligomer-induced impairment of spatial working memory in mice

P1-010: Native Aβ-oligomer-induced impairment of spatial working memory in mice

A 5-arm maze enables parallel measures of sustained visuo-spatial attention and spatial working memory in mice

A 5-arm maze has been developed to provide parallel tests of sustained visuo-spatial attention and spatial working memory in mice. C57Bl/6 mice were trained to select, either by immediate response (attention) or by delayed-matching response (working memory), one target arm among the five open arms. For attention testing, mice were first trained to acquire the basic task in which one randomly selected baited arm remained lit until a choice was made. Criterion of >80% correct with a response latency <5 s was attained in 52–56 trials. Following this, attention was tested by using trials wherein light signal durations of 2, 1 or 0.5 s were intermixed to vary attentional load. In the working memory test, mice were submitted to a forced visit to a randomly selected baited arm during a presentation phase. Following a variable retention interval (R.I.), mice were replaced into the maze and rewarded for choosing this arm. Criterion of >80% correct was attained in 35–40 trials and mice exhibited high levels of retention for R.I.s up to 4 h. Results validate the 5-arm maze for evaluation of both sustained visuo-spatial attention and spatial working memory in mice. Both the tasks are rapidly acquired and the 20% chance level provides high resolution for evaluating performance. This comparative strategy allows to dissociate attention and memory and to reveal deficits in these processes during ageing or in knockout strains. The high level of retention performance over R.I.s of 4 h enables studies using pharmacological treatments differentially affecting the acquisition, encoding, retention or retrieval phases of working memory. Furthermore, functional brain imaging studies may be used to identify neuronal networks which are differentially activated during these distinct phases.

Korean red ginseng saponins with low ratios of protopanaxadiol and protopanaxatriol saponin improve scopolamine-induced learning disability and spatial working memory in mice

The effects of two ginseng saponins having a different ratio of protopanaxadiol (PD) and protopanaxatriol saponins (PT) on the learning impairment induced by scopolamine, and learning and memory in mice were investigated in a passive avoidance task and a Morris water maze task. The ratio of PD and PT was 1.24 and 1.46, respectively. Before training, the ginseng saponins were administered intraperitoneally at doses of 50 and 100 mg/kg. The two saponins improved the scopolamine-induced learning impairment at different dosages in mice, 50 and 100 mg/kg, respectively. However, the two saponins did not show a favorable effect on learning and memory in normal mice. Korean red ginseng saponin with a low PD/PT ratio had an improving effect on spatial working memory, but the saponin with a high PD/PT ratio did not. This finding suggests that the PD/PT ratio of the ginseng saponins may be an important factor in the pharmacological role of red ginseng as a medicinal herb.

Role of nitric oxide and cyclic GMP in the dizocilpine-induced impairment of spontaneous alternation behavior in mice

The activation of N-methyl- d-aspartate receptors induces the synthesis of nitric oxide, which activates soluble guanylate cyclase and leads to the formation of cyclic GMP in the brain. The inhibition of nitric oxide production, as well as the blockade of N-methyl- d-aspartate receptors, has been reported to prevent the induction of hippocampal long-term potentiation and learning and memory formation in vivo, although the effects of inhibitors of nitric oxide synthase are still controversial. We investigated the putative role of nitric oxide and cyclic GMP in dizocilpine-induced memory impairment in mice. The nitric oxide synthase inhibitors, N G-nitro- l-arginine methyl ester and 7-nitro indazole, as well as dizocilpine, a non-competitive N-methyl- d-aspartate receptor antagonist, dose-dependently impaired spatial working memory in mice, assessed by their spontaneous alternation behavior in a Y-maze. The inhibitory effects of both N G-nitro- l-arginine methyl ester and dizocilpine on their behavior were completely reversed by 8-bromo-cyclic GMP. Cyclic GMP levels in the cerebellum were reduced by treatment with dizocilpine. N G-Nitro- l-arginine methyl ester and 7-nitro indazole reduced cyclic GMP levels in the cerebral cortex/hippocampus and cerebellum, and the suppressive effect of N G-nitro- l-arginine methyl ester on cyclic GMP levels in the cerebral cortex/hippocampus was reversed by co-treatment with l-arginine. Cyclic AMP levels in the brain were not affected by treatment with either dizocilpine, N G-nitro- l-arginine methyl ester, or 7-nitro indazole. Neither N G-nitro- l-arginine methyl ester nor l-arginine had any effect on monoamine and acetylcholine metabolism in the brain. These results suggest that the reduction in nitric oxide/cyclic GMP production in the brain may be responsible for dizocilpine-induced impairment of spontaneous alternation behavior in a Y-maze.