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Dräger et al. establish a rapid, scalable platform for iPSC-derived microglia. CRISPRi/a screens uncover roles of disease-associated genes in phagocytosis, and regulators of disease-relevant microglial states that can be targeted pharmacologically.
The mechanisms underlying neuron specification and maturation are unclear. Here the authors provide an integrated epigenomic and transcriptomic analysis of mouse and marmoset neocortical neuronal classes. Pan-neuronal programs active during early development are more evolutionary conserved but not neuron-specific, whereas pan-neuronal programs active during later stages of maturation are more neuron- and species-specific.
Bryois et al. mapped genetic variants regulating gene expression in eight major brain cell types. They found a large number of cell-type-specific genetic effects and leveraged their results to identify novel putative risk genes for brain disorders.
Moscarello and Penzo propose that mutually inhibitory circuits within the central nucleus of the amygdala implement a ‘winner-takes-all’ mechanism that guides transitions across defensive modes defined by threat-imminence theory.
Consumption of excessive high-fat diet (HFD) induces compulsive feeding. Here the authors show HFD-induced microglia activation in the anterior paraventricular nucleus of the thalamus plays a crucial role in promoting compulsive eating behavior.
Mouse models expressing liver apoE in the absence of brain apoE reveal detrimental effects of peripheral apoE4 associated with Alzheimer’s risk on cognition and amyloid pathology through compromising vascular integrity and function.
Studying the natural wanderings of the living brain is extremely challenging. Bolt et al. describe a new framework for considering the brain’s intrinsic activity based on the geophysical concepts of standing and traveling waves.
Kutlu, Zachry, Melugin et al. show that dopamine in the nucleus accumbens core is evoked by novel, neutral stimuli and tracks stimulus familiarity in the absence of valence-based predictions. These signals influence the speed of future learning for familiar stimuli.
The whole-brain organization of functional MRI signals has been studied in myriad ways. An in-depth study of these signals suggests a parsimonious description with a small number of spatiotemporal patterns.
Frontotemporal dementia (FTD) is a common early-onset dementia caused by heterozygous mutations in the progranulin gene (GRN). Gerrits et al. demonstrate blood–brain barrier dysfunction and a severely affected neurovasculature in FTD-GRN.
The language network in the brain shows similar properties across 45 languages spanning 12 language ‘families’. The language areas are lateralized to the left hemisphere, selective for language, and strongly functionally inter-connected. Variability among speakers of different languages is similar to the variability that has been reported among English speakers.
fMRI reveals similar topography, selectivity and inter-connectedness of language brain areas across 45 languages. These properties may allow the language system to handle the shared features of languages, shaped by biological and cultural evolution.
