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.

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.

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.

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.

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.

The authors show that Mrgprs, vagal sensory neuron-expressing GPCRs, mediate bronchoconstriction and hyperresponsiveness, both of which are hallmark features of asthma. The results reveal novel potential neural mechanisms underlying asthma.

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.

Direct neuronal conversion of skin fibroblasts from individuals with Huntington’s disease (HD) generates a population of medium spiny neurons that recapitulate hallmarks of HD, including aggregation of mutant huntingtin protein, DNA damage and spontaneous cell death.

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.

This study finds the key neurons that respond to 3D objects in the medial preoptic area (MPA). Their photostimulation induces hunting-like behaviors towards toys and prey, showing how the brain organizes behaviors to acquire useful resources.

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.

Neurons in the ventral hippocampus project to parvalbumin inhibitory interneurons in the infralimbic (IL) region of medial prefrontal cortex. Activation of this projection produces feed-forward inhibition of IL and causes relapse of extinguished fear.

In mice, stress-induced priming of glutamate synapses in the PVN can be transmitted through social interactions. This requires PVN CRH neuron activation in both of the interacting mice and release of an alarm pheromone from the stressed mouse.

Determining how to respond to others in distress is central to social cognition. In a new model, male rats approach stressed juveniles but avoid stressed adults; these behaviors require excitatory action of oxytocin within the insular cortex.

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.

Using longitudinal multimodal imaging data collected in healthy older individuals, Jacobs et al. provide in vivo evidence in humans that amyloid deposition facilitates tau spread along connected pathways and memory decline.

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.

dCas9-mediated activation has been verified and widely used in vitro. Here the authors generated a potent in vivo activation platform and applied it to control the transcription of multiple genetic elements in the mammalian brain.

CRISPR interference-based gene silencing was adopted to achieve highly efficient multiple and conditional gene knockdown in the mouse brain with negligible off-target effects, providing a rapid gene interrogation tool in the mammalian brain.