Single-cell and single-nucleus genomics pave the way for a comprehensive understanding of the nervous system and its diverse cell populations. Realizing this potential depends on meticulous planning, execution, and analysis. In this Focus Issue, three reviews from leaders in the field summarize best practices. The cover illustration symbolizes this effort with two hands pulling on a string, unraveling the complexity of the nervous system.

See Gokce et al. , Nowakowski et al. and Liddelow et al.

In this issue, Pritschet and colleagues offer a detailed map of a female human brain across gestation. Pronounced changes in gray and white matter demonstrate the brain’s capacity for extensive remodeling well into adulthood, paralleling the steep rise in hormone production. Reminiscent of sculpting marble, pregnancy is a transformative period of honing and refinement within the brain.

See Pritschet et al.

Neural dynamics are complex and simultaneously relate to distinct behaviors. To address these challenges, Sani et al. have developed an AI framework termed DPAD that achieves nonlinear dynamical modeling of neural–behavioral data, dissociates behaviorally relevant neural dynamics, and localizes the source of nonlinearity in the dynamical model. In the cover image, what DPAD does is visualized as separating the ovsubbed erall brain activity into distinct pieces related to specific behaviors and discovering how these pieces fit together to build the overall activity.

See Sani et al.

Coughing is a vital respiratory defense mechanism. Gannot et al. identified a genetically defined neural circuit connecting the airway to the brain that controls cough-like behavior in mice. The cover art features a mouse coughing, with a brain image illustrated in the droplets. The key brain region for coughing, the nucleus of the solitary tract, is highlighted in white.

See Peng Li et al.

Communication between glial cells has a profound effect on the pathophysiology of Alzheimer’s disease. Huang et al. report that reactive astrocytes impose cell distancing in peri-plaque glial nets via the guidance receptor Plexin-B1, which affects microglial access and compaction of amyloid plaques. The cover art depicts a fishing net catching fish, which symbolizes glial nets surrounding amyloid deposits in Alzheimer’s disease.

See Huang et al.

Our growing understanding of cell diversity generates an increasing need for molecular tools that selectively target cells on the basis of multiple features. Hughes et al. present an AAV-based toolkit that uses hammerhead ribozymes to achieve intersectional transgene expression. In the cover image, overlapping vinyl records form an abstract representation of Venn diagrams that highlight the intersectionality of complex features.

See Hughes et al.

Racial health disparities are shaped by complex interactions among genetics and the environment . Benjamin et al. investigate differential brain gene expression and epigenetic modifications linked to ancestry variation among Black Americans, and how these relate to risks for various brain illnesses and traits.

See Benjamin et al.

Chemicals in household products may affect brain development through direct toxic effects on oligodendrocytes, the myelinating cells in the central nervous system. These chemicals can be found in many consumer products, including hair conditioners, disinfecting wipes, and mouthwash. Because oligodendrocytes can develop and myelinate throughout childhood, the chemicals may pose a significant health risk to children. This image depicts a setting in which a child may be exposed to the identified chemicals. In this image, a myelinated neuron and oligodendrocytes float in the water of a bathtub, where they are covered in quaternary compounds.

See Cohn et al.

The molecular identity of cold sensors in peripheral somatosensory neurons remains unclear. Cai et al. report that GluK2, a kainate-type glutamate receptor that mediates synaptic transmission in the brain, is co-opted as a cold sensor in the periphery. The cover art depicts snow and ice adhering to the ends of branches, symbolizing the role of peripheral sensory nerve endings, distant from the soma (shown in the background), as the primary detectors of cold.

See Cai et al.

Within the enigmatic depths of an aquatic universe, divers use flashlights to reveal the hidden contours of an uncharted seabed that teems with wondrous vegetation. In an analogous exploration, Hollunder et al. describe how invasive brain stimulation delivered to deep-seated brain nuclei may act as a beacon. Using deep brain stimulation (DBS), they show that the frontal cortex can be segregated into distinct circuits that become dysfunctional in four different brain disorders. Their topographical map may shed light on more-precise brain-circuit therapeutics.

See Hollunder, et al.

During gestation, childbirth, and the postpartum period, dynamic cortical plasticity occurs in mothers’ brains. Paternina-Die, Martínez-García et al. show decreased cortical thickness during pregnancy, which attenuates after birth. In the cover image, the mantle enveloping the mother with child symbolizes the cortical mantle, and the shape of the woman’s brain resembles a baby, serving as a metaphor for the maternal brain. The pixelation overlaying the baby and the background recreates the MRI voxels. The central figure in the image portrays Dr Paternina-Die, who herself became a first-time mother during the completion of this study.

See Paternina-Die, Martínez-García, et al.

To maximize fitness, most animals adopt an optimal foraging strategy to procure the highest energy at the lowest cost. For example, nighttime is likely to be preferred by nocturnal animals owing to its relative safety from predators and the ease of food availability. In an environment with such periodic food availability, AgRP neurons are entrained by past successful feeding experiences and use this circadian information to promote foraging at similar time windows on subsequent days to maximize the chance of feeding.

See Sayar-Atasoy et al.