Tau in cerebrospinal fluid induces neuronal hyperexcitability and alters hippocampal theta oscillations

Alzheimer’s disease (AD) and other tauopathies are characterized by the aggregation of tau into soluble and insoluble forms (including tangles and neuropil threads). In humans, a fraction of both phosphorylated and non-phosphorylated N-terminal to mid-domain tau species, are secreted into cerebrospinal fluid (CSF). Some of these CSF tau species can be measured as diagnostic and prognostic biomarkers, starting from early stages of disease. While in animal models of AD pathology, soluble tau aggregates have been shown to disrupt neuronal function, it is unclear whether the tau species present in CSF will modulate neural activity. Here, we have developed and applied a novel approach to examine the electrophysiological effects of CSF from patients with a tau-positive biomarker profile. The method involves incubation of acutely-isolated wild-type mouse hippocampal brain slices with small volumes of diluted human CSF, followed by a suite of electrophysiological recording methods to evaluate their effects on neuronal function, from single cells through to the network level. Comparison of the toxicity profiles of the same CSF samples, with and without immuno-depletion for tau, has enabled a pioneering demonstration that CSF-tau potently modulates neuronal function. We demonstrate that CSF-tau mediates an increase in neuronal excitability in single cells. We then observed, at the network level, increased input–output responses and enhanced paired-pulse facilitation as well as an increase in long-term potentiation. Finally, we show that CSF-tau modifies the generation and maintenance of hippocampal theta oscillations, which have important roles in learning and memory and are known to be altered in AD patients. Together, we describe a novel method for screening human CSF-tau to understand functional effects on neuron and network activity, which could have far-reaching benefits in understanding tau pathology, thus allowing for the development of better targeted treatments for tauopathies in the future. Graphical Abstract: [Figure not available: see fulltext.

Temporal variation in black-caiman-nest predation in varzea of central Brazilian amazonia

On the Amazon floodplain, the main predators of black caiman (Melanosuchus niger) eggs are jaguars (Panthera onca), tegu lizards (Tupinambis teguixim), capuchin monkeys (Sapajus macrocephalus) and humans (Homo sapiens). In this study, we investigated the relationship between predator attacks on nests and incubation period, and evaluated the influence of initial predation on subsequent predation in the Mamirauá Sustainable Development Reserve. We also evaluated the influence of presence of females near the nests and manipulation of nests on the occurrence of attacks. We compared results from data obtained with camera traps and vestiges left by predators on estimates of rates of predation by different predators. Egg predation was recorded in 32% of the 658 black caiman nests monitored during two years. Our results suggest that the probability of predation on black caiman eggs is relatively constant throughout the incubation period and that predation on eggs was lower when adults, presumably females, were present. Careful opening of nests and handling of eggs did not increase the number of attacks on black caiman nests. Nest opening by a predator appeared to increase the chances of a subsequent attack because most of the attacks on nests occurred soon after a predator first opened the nest. However, attacks by another species of predator do not appear to be necessary to initiate attacks by any other species of predator. Results based on camera traps and vestiges differed, but use of vestiges was adequate for identifying the principal predators on eggs in black caiman nests and, in many circumstances, the vestiges may be better for estimating predation by humans. In this study, opening nests and handling eggs did not increase the number of attacks on black caiman nests. © 2017 Torralvo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited