Yu et al. identify two serotonergic pathways from the dorsal raphe nucleus to the basal amygdala that are differentially involved in the regulation of anxiety-related social avoidance and the avoidance of bright spaces. This finding is depicted on the cover by showing a spotlight on a mouse that creates shadows of different anxiety-related mouse postures and two different neuron-like halos.

See Yu et al.

Morizawa and colleagues show that motor learning induces synapse engulfment and nibbling of dendritic spines by Bergmann glia. The magenta buds represent Purkinje cell dendritic spines. The bird represents Bergmann glia, nibbling dendritic spines.

See Morizawa et al.

Compared to the awake state, anesthesia drastically changes similarity relationships between activity patterns that represent sounds and spontaneous activity. Reflection distortions on convex mirrors change the scope and amplify the most prominent changes induced by anesthesia in the cortex (above) and thalamus (below).

See Filipchuk et al.

Georgiou et al. find that the sex of the person performing experiments affects mouse behavior, including responses to stress and ketamine. This effect is mediated by CRF neurons in the entorhinal cortex that project to CA1.

See Georgiou et al.

Kjaerby, Andersen and colleagues show that extracellular levels of norepinephrine slowly oscillate during sleep, causing alternations between arousal and memory-consolidating sleep stages. This is illustrated on the cover, which shows waves of norepinephrine with sleeping people floating on top.

See Kjaerby et al.

How does sleep affect sensory responses? Hayat and colleagues recorded intracranial electrophysiology and neuron activity in sleeping humans while playing sounds, which revealed robust cortical responses and impaired neuronal feedback signaling. The cover art illustrates how an external event (the shooting star) triggers some response in the sleeping brain (lit stars) while leaving other aspects of the response inactive (dark stars).

See Hayat et al.

By fluorescently tagging the autophagy ‘waste recycling’ pathway in neurons in the brains of mouse models of Alzheimer’s disease (AD), Lee and colleagues visualized a massive build-up of waste-filled vacuoles that cause the neurons’ circumferences to bulge in a unique flower-like pattern. These vacuoles, which contain forms of amyloid-ß, also coalesce centrally around the (DAPI-blue stained) nucleus, generating a senile (amyloid) plaque within the still-intact neuron. The rosettes of fluorescent protrusions from the cell membrane surface (blebs) are packed with autophagic vacuoles tagged by eGFP–mRFP–LC3; imaged on a section of cortex from the 5xFAD mouse model of AD.

See Lee et al.

Mazzitelli and Smyth et al. describe a previously unrecognized form of neuroimmune communication whereby cerebrospinal fluid gains direct access to skull bone marrow niches to regulate meningeal immune supply. Cerebrospinal fluid, like a river rushing and flowing from afar, carries CNS-derived signals to skull bone marrow reservoirs.

See Mazzitelli et al.

Gao and colleagues developed an efficient pipeline for constructing single-neuron projectomes and built a database of 6,357 single-neuron projectomes of mouse prefrontal cortex (PFC), from which they defined 64 projectome-defined neuron subtypes, topographic organization of PFC axon projections, modular structure within PFC, and correspondence with transcriptomes. The image illustrates the whole-brain axon projections of selected reconstructed neurons across PFC.

See Gao et al.

Ratz et al. present a robust method to barcode progenitor cells, enabling profiling of cell phenotypes and clonal relations using single-cell and spatial transcriptomics to provide an integrated approach for understanding brain architecture. The cover art illustrates uniquely barcoded progenitor cells that develop into a range of diverse cell types.

See Ratz et al.

Le and colleagues present evidence that, within the hippocampus, synaptic plasticity and learning thresholds change in opposite directions between males and females in the transition to post-pubertal life. This is represented by dendrites and the glowing dendritic spines denoting synaptic signaling. The dendrites are approached by seahorses (hippocampi) in different stages of development, with blue and pink hues indicating their sexes.

See Le et al.

By solving the complex structures of third-generation antipsychotic drugs (TGAs) with the 5HT2A receptor, Chen et al. unravel their unique pharmacology and design a novel TGA lead that has cognition-improving and potential antidepressant properties.

See Chen et al.