Adaptation of the Arizona Cognitive Task Battery for use with the Ts65Dn mouse model (Mus musculus) of Down syndrome.

We propose and validate a clear strategy to efficiently and comprehensively characterize neurobehavioral deficits in the Ts65Dn mouse model of Down syndrome. This novel approach uses neurocognitive theory to design and select behavioral tasks that test specific hypotheses concerning the results of Down syndrome. In this article, we model the Arizona Cognitive Task Battery, used to study human populations with Down syndrome, in Ts65Dn mice. We observed specific deficits for spatial memory, impaired long-term memory for visual objects, acquisition and reversal of motor responses, reduced motor dexterity, and impaired adaptive function as measured by nesting and anxiety tasks. The Ts65Dn mice showed intact temporal ordering, novelty detection, and visual object recognition with short delays. These results phenocopy the performance of participants with Down syndrome on the Arizona Cognitive Task Battery. This approach extends the utility of mouse models of Down syndrome by integrating the expertise of clinical neurology and cognitive neuroscience into the mouse behavioral laboratory. Further, by directly emphasizing the reciprocal translation of research between human disease states and the associated mouse models, we demonstrate that it is possible for both groups to mutually inform each other's research to more efficiently generate hypotheses and elucidate treatment strategies. (PsycINFO Database Record

Patterns and scales of connectivity: temporal stability and variation within a marine metapopulation.

Because many marine invertebrates have a dispersive planktonic phase, the spatial scale of demographic, connectivity among local populations remains a key, but elusive, parameter driving population and metapopulation dynamics. However, temporal variation in the scale of connectivity remains largely undocumented, despite its recognized importance for predicting population responses to environmental changes. To assess the temporal stability of metapopulation connectivity, we conducted a large-scale survey of a blue mussel (Mytilus spp.) metapopulation for five years along a 100-km section of coastline of the Gaspé Peninsula, Québec, Canada. For each year, we estimated the scale of demographic coupling among 27-29 sites within our study region, using the spatial cross-covariance between adult abundance and recruit density across sites. Despite large interannual variability in overall recruit abundance, our analysis revealed stationary spatial distributions of adult and recruit abundance. More importantly, our analysis revealed a consistent demographic coupling among populations at a distance ranging from 12 to 24 km in all but one of the five years studied. The scale of connectivity in this system is thus temporally stable, but can occasionally show irregular fluctuations, and our results provide evidence in support of the integration of time-varying connectivity to marine metapopulation and reserve network theories.

Dentate gyrus mediates cognitive function in the Ts65Dn/DnJ mouse model of Down syndrome.

In the Ts65Dn/DnJ mouse model of Down syndrome (DS), hippocampal deficits of learning and memory are the most robust features supporting this mouse as a valid cognitive model of DS. Although dentate gyrus (DG) dysfunction is suggested by excessive GABAergic inhibition, its role in perturbing DG functions in DS is unknown. We hypothesize that in the Ts65Dn/DnJ mouse, the specific role of the DG is disturbed in its support of contextual and spatial information. Support for this hypothesis comes from rats with DG lesions that show similar deficits. In order to test this hypothesis, we have developed a novel series of spontaneous exploratory tasks that emphasize the importance of recognizing spatial and contextual cues and that involve DG function. The results with this exploratory battery show that Ts65Dn/DnJ mice are impaired in DG-dependent short-term recognition tests involving object recognition with contextual cues, in place recognition and in metric distance recognition relative to wild type littermate controls. Further, whereas Ts65Dn/DnJ mice can recognize object novelty in the absence of contextual cues after a 5-min delay, they cannot do so after a delay of 24 h, suggesting a problem with CA1-mediated consolidation. The results also show that Ts65Dn/DnJ mice are not impaired in tasks (object recognition and configural object recognition) that are mediated by the perirhinal cortex (PRh). These results implicate the DG as a specific therapeutic target and the PRh as a potential therapeutic strength for future research to ameliorate learning and memory in DS.