Astrocyte calcium dysfunction causes early network hyperactivity in Alzheimer's disease

Dysfunctions of network activity and functional connectivity (FC) represent early events in Alzheimer's disease (AD), but the underlying mechanisms remain unclear. Astrocytes regulate local neuronal activity in the healthy brain, but their involvement in early network hyperactivity in AD is unknown. We show increased FC in the human cingulate cortex several years before amyloid deposition. We find the same early cingulate FC disruption and neuronal hyperactivity in AppNL-F mice. Crucially, these network disruptions are accompanied by decreased astrocyte calcium signaling. Recovery of astrocytic calcium activity normalizes neuronal hyperactivity and FC, as well as seizure susceptibility and day/night behavioral disruptions. In conclusion, we show that astrocytes mediate initial features of AD and drive clinically relevant phenotypes

Report A Multivariate Approach Reveals the Behavioral Templates Underlying Visual Discrimination in Rats

Summary Although rodents are the first-choice animal model in the life sciences, they are rarely used to study higher visual functions. It is unclear to what extent rodents follow complex visual strategies to solve visual object recognition and discrimination tasks Results and Discussion Behavioral Templates in Rats Five rats were trained to discriminate a square from a triangle. Although object recognition in general is a well-studied capacity in rats We were able to extract templates that identified stimulus locations affecting task performance (Cluster test with threshold set at 2.7, see To what degree can performance be explained by a simple strategy such as ''the square is at the side that is brighter at the bottom''? We modeled this ''bright below = square'' strategy by comparing the average luminance pattern of both stimuli, weighted with a vertical gradient decreasing from bottom to top (see A Flexible, Context-Dependent Strategy Is Revealed by Conditional Templates A common characteristic of this subset of trials on which a simple ''bright below = square'' strategy fails, is that the bottom of the shapes was covered by bubbles. Given that in these trials the bubbles mostly cover the significant areas in the behavioral templates, we next investigated which image areas were being used by the animals. Hence we constructed ''conditional'' templates using only the subset of the trials on which the ''bright below = square'' strategy fails. As shown i

Quality System Implementation in Member States of the IAEA.

Abstract not availableJRC.D-Institute for Reference Materials and Measurements (Geel

Study of the double beta decays of 96Ru and 104Ru

In this work we present new improved experimental limits for the partial half-lives of the double beta processes of 96Ru and 104Ru, obtained by means of a gamma-spectrometry measurement. A disc of metallic Ru of natural isotopic abundance was sandwiched between two HPGe-detectors in the 225 m deep underground laboratory HADES. After 50 days of measurement, the lower bounds for the partial half-lives were up to 6×1019 yr for 96Ru and 1.6×1020 yr for 104Ru.JRC.D.4-Nuclear physic

Neutron spectrum calibration using the Cd-ratio for multi-monitor method with a synthetic multi-element standard

Several methods are in use for the determination of the thermal to epithermal neutron fluence rate ratio (f) and the deviation of the epithermal neutron spectrum from the 1/E shape parameter (alpha). In our former work, it was proven that the recently developed and characterized Synthetic Multi-ELement Standard (SMELS) can be used for the fast verification of the stability of the irradiation parameters using the Au-Zr bare monitor method. However, this latter method using SMELS had a too low precision for an accurate determination of f and alpha. Therefore, the Cd-ratio for multi-monitor method using SMELS was investigated for two irradiation channels. As shown the material can also be used as a monitor for the calibration of an irradiation facility