Hippocampal reactivation of random trajectories resembling Brownian Diffusion

Hippocampal activity patterns representing movement trajectories are reactivated in immobility and sleep periods, a process associated with memory recall, consolidation, and decision making. It is thought that only fixed, behaviorally relevant patterns can be reactivated, which are stored across hippocampal synaptic connections. To test whether some generalized rules govern reactivation, we examined trajectory reactivation following non-stereotypical exploration of familiar open-field environments. We found that random trajectories of varying lengths and timescales were reactivated, resembling that of Brownian motion of particles. The animals’ behavioral trajectory did not follow Brownian diffusion demonstrating that the exact behavioral experience is not reactivated. Therefore, hippocampal circuits are able to generate random trajectories of any recently active map by following diffusion dynamics. This ability of hippocampal circuits to generate representations of all behavioral outcome combinations, experienced or not, may underlie a wide variety of hippocampal-dependent cognitive functions such as learning, generalization, and planning

Assembly responses of hippocampal CA1 place cells predict learned behavior in goal-directed spatial tasks on the radial eight-arm maze

Hippocampus is needed for both spatial working and reference memories. Here, using a radial eight-arm maze, we examined how the combined demand on these memories influenced CA1 place cell assemblies while reference memories were partially updated. This was contrasted with control tasks requiring only working memory or the update of reference memory. Reference memory update led to the reward-directed place field shifts at newly rewarded arms and to the gradual strengthening of firing in passes between newly rewarded arms but not between those passes that included a familiar-rewarded arm. At the maze center, transient network synchronization periods preferentially replayed trajectories of the next chosen arm in reference memory tasks but the previously visited arm in the working memory task. Hence, reference memory demand was uniquely associated with a gradual, goal novelty-related reorganization of place cell assemblies and with trajectory replay that reflected the animal’s decision of which arm to visit next

The effect of testosterone and a nutritional supplement on hospital admissions in under-nourished, older people

Extent: 8p.Background: Weight loss and under-nutrition are relatively common in older people, and are associated with poor outcomes including increased rates of hospital admissions and death. In a pilot study of 49 undernourished older, community dwelling people we found that daily treatment for one year with a combination of testosterone tablets and a nutritional supplement produced a significant reduction in hospitalizations. We propose a larger, multicentre study to explore and hopefully confirm this exciting, potentially important finding (NHMRC project grant number 627178). Methods/Design: One year randomized control trial where subjects are allocated to either oral testosterone undecanoate and high calorie oral nutritional supplement or placebo medication and low calorie oral nutritional supplementation. 200 older community-dwelling, undernourished people [Mini Nutritional Assessment score 7.5% over 3 months)]. Hospital admissions, quality-adjusted life years, functional status, nutritional health, muscle strength, body composition and other variables will be assessed. Discussion: The pilot study showed that combined treatment with an oral testosterone and a supplement drink was well tolerated and safe, and reduced the number of people hospitalised and duration of hospital admissions in undernourished, community dwelling older people. This is an exciting finding, as it identifies a treatment which may be of substantial benefit to many older people in our community. We now propose to conduct a multi-centre study to test these findings in a substantially larger subject group, and to determine the cost effectiveness of this treatment. Trial registration: Australian Clinical Trial Registry: ACTRN 12610000356066Cynthia Piantadosi, Renuka Visvanathan, Vasi Naganathan, Peter Hunter, Ian D. Cameron, Kylie Lange, Jonathan Karnon and Ian M. Chapma