Microglia are active players in inflammation, but also have important supporting roles in CNS maintenance and function, including modulation of neuronal activity. We previously observed an increase in the frequency of excitatory postsynaptic current in organotypic brain slices after depletion of microglia using clodronate. Here, we describe that local hippocampal depletion of microglia by clodronate alters performance in tests of spatial memory and sociability. Global depletion of microglia by high-dose oral administration of a Csf1R inhibitor transiently altered spatial memory but produced no change in sociability behavior. Microglia depletion and behavior effects were both reversible, consistent with a dynamic role for microglia in the regulation of such behaviors.

Alzheimer’s disease (AD) is an age-dependent neurodegenerative condition that causes a progressive decline in cognitive function. Accumulation of amyloid β-protein (Aβ) in the brain is a prominent feature of AD and related disorders. The levels of Aβ accumulation alone are not a reliable predictor of cognitive deficits, which suggests other factors such as location of deposition may be more important. Aβ accumulates in AD brain in the form of parenchymal amyloid plaques and cerebral vascular deposits. Although both types of lesions can contribute to cognitive decline their temporal impact remains unclear. Moreover, cerebral microvascular pathology is identified as an early driver of cognitive impairment. Here for the first time, we compared two transgenic mouse strains, Tg-5xFAD and Tg-SwDI, which exhibit similar onset and anatomical accumulation of Aβ, but with distinct parenchymal and microvascular compartmental amyloid deposition, to assess the impact of their respective pathologies on cognitive impairment. Cohorts of each line were tested at 3 and 6 months of age to assess the relationship between spatial working memory and quantitative Aβ pathology. At 3 months of age, Tg-SwDI mice with onset of cerebral microvascular amyloid were behaviorally impaired, while the Tg-5xFAD, which had disproportionately higher levels of total Aβ, soluble oligomeric Aβ, and parenchymal amyloid were not. However, at 6 months of age, behavioral deficits for both groups of transgenic mice were evident, as the levels of Aβ pathologies in the Tg-5xFAD accumulated to extremely high amounts. The present findings suggest that early-onset cerebral microvascular amyloid deposition, that precedes high parenchymal levels of Aβ, may be an important early factor in the development of cognitive deficits. Key words: amyloid β protein; cerebral microvascular, parenchymal, pathology, cognitive impairment, transgenic mice

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Cardiovascular exercise (CVE) is associated with healthy aging and reduced risk of disease in humans, with similar benefits seen in animals. Most rodent studies, however, have used shorter intervention periods of a few weeks to a few months, begging questions as to the effects of longer-term, or even life-long, exercise. Additionally, most animal studies have utilized a single exercise treatment group - usually unlimited running wheel access - resulting in large volumes of exercise that are not clinically relevant. It is therefore incumbent to determine the physiological and cognitive/behavioral effects of a range of exercise intensities and volumes over a long-term period that model a lifelong commitment to CVE. In the current study, C57/Bl6 mice remained sedentary or were allowed either 1, 3, or 12 h of access to a running wheel per day, 5 days/weeks, beginning at 3.5-4 months of age. Following an eight-month intervention period, animals underwent a battery of behavioral testing, then euthanized and blood and tissue were collected. Longer access to a running wheel resulted in greater volume and higher running speed, but more breaks in running. All exercise groups showed similarly reduced body weight, increased muscle mass, improved motor function on the rotarod, and reduced anxiety in the open field. While all exercise groups showed increased food intake, this was greatest in the 12 h group but did not differ between 1 h and 3 h mice. While exercise dose-dependently increased working memory performance in the y-maze, the 1 h and 12 h groups showed the largest changes in the mass of many organs, as well as alterations in several behaviors including social interaction, novel object recognition, and Barnes maze performance. These findings suggest that long-term exercise has widespread effects on physiology, behavior, and cognition, which vary by "dose" and measure, and that even relatively small amounts of daily exercise can provide benefits.

In cooperative multirobot systems, communication can speed up completion, reduce redundancy, and prevent interference between robots. Typically, wireless point-to-point communication is used to coordinate robots. However, environmental interference, unpredictable network conditions, and distances between robots can affect the reliability of wireless communication. Therefore, approaches other than continuous message passing throughout exploration are useful.We consider the problem of coordinating a multirobot system to explore an unknown, large, open environment. An approach that uses sector search with rendezvous is presented. Robots explore an environment in sectors, or designated areas, and periodically meet to communicate map information of what they have explored. Our approach is compared to other communication paradigms in simulation. Results suggest that sector search with rendezvous is more efficient than having no communications. It further demonstrates advantages over scenarios in which robots communicate only with other robots in close proximity, and is comparable to a role-based approach with dynamic team hierarchies.