Microglia are the main immune cells in the brain and have roles in brain homeostasis and neurological diseases. Mechanisms underlying microglia–neuron communication remain elusive. Here, we identified an interaction site between neuronal cell bodies and microglial processes in mouse and human brain. Somatic microglia–neuron junctions have a specialized nanoarchitecture optimized for purinergic signaling. Activity of neuronal mitochondria was linked with microglial junction formation, which was induced rapidly in response to neuronal activation and blocked by inhibition of P2Y12 receptors. Brain injury–induced changes at somatic junctions triggered P2Y12 receptor–dependent microglial neuroprotection, regulating neuronal calcium load and functional connectivity. Thus, microglial processes at these junctions could potentially monitor and protect neuronal functions.

We report second-order rate constants kDO (M-1 s-1) for exchange for deuterium of the C(2)-proton of a series of simple imidazolium cations to give the corresponding singlet imidazol-2-yl carbenes in D2O at 25 degrees C and I = 1.0 (KCl). Evidence is presented that the reverse protonation of imidazol-2-yl carbenes by solvent water is limited by solvent reorganization and occurs with a rate constant of kHOH = kreorg = 10(11) s-1. The data were used to calculate reliable carbon acid pK(a)s for ionization of imidazolium cations at C(2) to give the corresponding singlet imidazol-2-yl carbenes in water: pKa = 23.8 for the imidazolium cation, pKa = 23.0 for the 1,3-dimethylimidazolium cation, pKa = 21.6 for the 1,3-dimethylbenzimidazolium cation, and pKa = 21.2 for the 1,3-bis-((S)-1-phenylethyl)benzimidazolium cation. The data also provide the thermodynamic driving force for a 1,2-hydrogen shift at a singlet carbene: K12 = 5 x 10(16) for rearrangement of the parent imidazol-2-yl carbene to give neutral imidazole in water at 298 K, which corresponds to a favorable Gibbs free energy change of 23 kcal/mol. We present a simple rationale for the observed substituent effects on the thermodynamic stability of N-heterocyclic carbenes relative to a variety of neutral and cationic derivatives that emphasizes the importance of the choice of reference reaction when assessing the stability of N-heterocyclic carbenes.

Computer-based assessment can provide new insights into behavioral processes of task completion that cannot be uncovered by paper-based instruments. Time presents a major characteristic of the task completion process. Psychologically, time on task has 2 different interpretations, suggesting opposing associations with task outcome: Spending more time may be positively related to the outcome as the task is completed more carefully. However, the relation may be negative if working more fluently, and thus faster, reflects higher skill level. Using a dual processing theory framework, the present study argues that the validity of each assumption is dependent on the relative degree of controlled versus routine cognitive processing required by a task, as well as a person's acquired skill. A total of 1,020 persons ages 16 to 65 years participated in the German field test of the Programme for the International Assessment of Adult Competencies. Test takers completed computer-based reading and problem solving tasks. As revealed by linear mixed models, in problem solving, which required controlled processing, the time on task effect was positive and increased with task difficulty. In reading tasks, which required more routine processing, the time on task effect was negative and the more negative, the easier a task was. In problem solving, the positive time on task effect decreased with increasing skill level. In reading, the negative time on task effect increased with increasing skill level. These heterogeneous effects suggest that time on task has no uniform interpretation but is a function of task difficulty and individual skill.There are two fundamental observations on human perfor mance: the result obtained on a task and the time taken (e.g., Ebel, 1953). In educational assessment, the focus is mainly on the task outcome; behavioral processes that led to the result are usually not considered. One reason may be that traditional assessments are paper-based and, hence, are not suitable for collecting behavioral process data at the task level (cf. Scheuermann & Bjomsson, 2009). However, computer-based assessment-besides other ad vantages, such as increased construct validity (e.g., Sireci & Zenisky, 2006) or improved test design (e.g., van der Linden, 2005)-can provide further insights into the task completion pro cess. This is because in computer-based assessment, log file data can be recorded by the assessment system that allows the re searcher to derive theoretically meaningful descriptors of the task completion process. The present study draws on log file data from an international computer-based large-scale assessment to address the question of how time on task is related to the task outcome. As shown in the following, by analyzing the relation of task perfor mance to the time test takers spent on task, we were able to obtain new insights into how the interaction of task and person charac-

Neurotropic herpesviruses can establish lifelong infection in humans and contribute to severe diseases including encephalitis and neurodegeneration. However, the mechanisms through which the brain’s immune system recognizes and controls viral infections propagating across synaptically linked neuronal circuits have remained unclear. Using a well-established model of alphaherpesvirus infection that reaches the brain exclusively via retrograde transsynaptic spread from the periphery, and in vivo two-photon imaging combined with high resolution microscopy, we show that microglia are recruited to and isolate infected neurons within hours. Selective elimination of microglia results in a marked increase in the spread of infection and egress of viral particles into the brain parenchyma, which are associated with diverse neurological symptoms. Microglia recruitment and clearance of infected cells require cell-autonomous P2Y12 signalling in microglia, triggered by nucleotides released from affected neurons. In turn, we identify microglia as key contributors to monocyte recruitment into the inflamed brain, which process is largely independent of P2Y12. P2Y12-positive microglia are also recruited to infected neurons in the human brain during viral encephalitis and both microglial responses and leukocyte numbers correlate with the severity of infection. Thus, our data identify a key role for microglial P2Y12 in defence against neurotropic viruses, whilst P2Y12-independent actions of microglia may contribute to neuroinflammation by facilitating monocyte recruitment to the sites of infection.Electronic supplementary materialThe online version of this article (10.1007/s00401-018-1885-0) contains supplementary material, which is available to authorized users.