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By comparing the genome-wide profile of H4K16ac in AD with younger and elder controls, the authors propose a mechanism for how age is a risk factor for AD: a histone modification, whose accumulation is associated with aging, is dysregulated in AD.
The authors developed a CUBIC tissue clearing and expansion method to generate an editable, point-based single-cell-resolution brain atlas. This atlas, termed CUBIC-Atlas, can be used for unbiased systems-level cellular analysis in whole mouse brain.
Myeloid cells are critical in the pathology of inflammatory and degenerative brain diseases. The authors use single-cell mass cytometry (CyTOF) to reveal distinct characteristics in these cells in models of neural inflammation and degeneration.
Rabies viral vectors are important tools in neuroscience, but their cytotoxicity usually limits their use. Chatterjee et al. introduce a new class of double-deletion-mutant rabies viral vectors that leaves neurons alive and healthy indefinitely.
Whether we currently pay attention to memory items matters for their neural representation. Unattended items are stored exclusively in activity of higher-level brain areas, whereas attended items are also represented in low-level sensory regions.
Intersectional gene ablation, pharmacology & song-triggered optogenetic stimulation of VTA terminals together show a common VTA–basal ganglia circuit enabling internally and externally guided juvenile song-copying and adult pitch learning in finches.
The way spike count variability is correlated between two neurons depends on the neurons' stimulus preferences. Here the authors show that this dependency itself varies systematically with behavioral task, implying a feedback origin of correlations.
The human brain shows regional selective vulnerability to the pathology of Alzheimer’s disease. Jacobs et al. show that the protein amyloid-β promotes the spread of tau through specific components of a neural system underlying memory formation, thus leading to the prominent early symptom of amnesia.
Humans and animals can react to the affective state of others in distress. However, exposure to a stressed partner can trigger stress-related adaptations. Two studies shed light on the mechanisms underlying the behavioral responses toward stressed individuals and on the synaptic changes associated with social transmission of stress.
Direct conversion of adult Huntington’s disease patient fibroblasts into medium spiny neurons recapitulates hallmark phenotypes such as cell death, in contrast to models that lack epigenetic markers of aging. This successful ‘disease-in-a-dish’ highlights the benefits of capturing age in an adult-onset disorder model.
Using a series of functional manipulation and in vivo recording tools, Park et al. identify a pathway from medial preoptic CaMKIIα-expressing neurons to the ventral periaqueductal gray that mediates object craving and prey hunting.
Microglia show remarkable regenerative capacity after acute depletion, which had been thought to be derived from de novo progenitors. Peng and colleagues demonstrate that the newly formed microglia are actually solely derived from residual microglia.
Using an inducible mouse model of sporadic ALS, Spiller et al. show that spinal microgliosis is not a major feature of TDP-43-triggered disease. Instead, microglia mediate TDP-43 clearance and motor recovery, suggesting a neuroprotective role in ALS.
Bloss et al. show single axons form clustered inputs onto the dendrites of hippocampal pyramidal cells in a projection-specific manner. The spatial and temporal features inherent in these connections efficiently drive dendritic depolarization.
New data reveal that the amygdala—a brain area specialized for emotion—also signals the hierarchical rank of peers in a social group. These neural signals likely mediate appropriate social and emotional behavior in many social settings.
The authors discuss newly emerging evidence for the role of the transcription factor CREB in memory, including its role in modulating changes in excitability that are critical for neural assembly formation and linking of memories across time.
This study describes single-nucleus ATAC-seq, a method to profile open chromatin in individual nuclei from frozen tissues. It is used to examine gene regulation in 15,000 nuclei comprising 20 distinct cell types in the developing mouse forebrain.
Addiction-related behaviors are believed to result from drug-evoked synaptic changes, but their causality is unclear. The authors show that bidirectional optogenetic modifications of synaptic strength distinctly alter alcohol-seeking behavior.
Research in adolescent neurocognitive development has focussed largely on averages, but there is substantial individual variation in development. This Perspective proposes that the field should move towards studying individual differences.