Choi et al. demonstrate that stroke disrupts temporal separability between beta and movement-related ensemble co-firing states, which is restored during recovery. They also show that low-frequency alternating current stimulation enhances separability, improves motor performance, and thus represents a promising therapeutic approach.

Through the perspective of metaplasticity, Brown et al. examine the therapeutic effects of intermittent ketamine administration and explore how targeting spatiotemporal features of antidepressant dosing and environmental conditions may improve the effectiveness of treatments for depression.

In this NeuroView, Giacomo Indiveri discusses the origins and evolution of neuromorphic engineering, reflects on recent shifts toward digital and AI-centric approaches, and advocates for a revival of the field’s original principles, emphasizing analog, brain-inspired systems and the importance of fundamental neuroscience for future progress.

Guo et al. identify the peptide Vulnusin as an acute wound signal that activates C4da nociceptors through the PPK1/PPK26 ion channel in Drosophila larvae. Vulnusin localizes in the extracellular space apical to the epidermis when uninjured but reaches the C4da nociceptor upon damage to trigger the nociceptive rolling behavior.

Luo et al. identify distinct supramammillary-dentate gyrus subcircuits that differentially regulate memory and emotion. In Alzheimer’s disease (AD) models, these pathways show aberrant activity, but targeted optogenetic activation selectively restores cognitive or affective functions, revealing circuit-level mechanisms underlying diverse AD symptoms and highlighting potential therapeutic targets.

Castelli et al. identify two ripple profiles in hippocampal CA1. Radsink ripples integrate superficial- and deep-sublayer pyramidal cells into dense, higher-dimensional coactivity motifs that stably reactivate recent waking experience during sleep. LMsink ripples primarily recruit deep-sublayer cells into sparse, lower-dimensional motifs that gradually drift from reactivating prior toward recent representations.

Kamath et al. examine the neural mechanism by which hunger makes animals take more risks. They show that hunger neurons in the hypothalamus suppress threat and salience-related dopamine signals in the tail of the striatum during bouts of novelty exploration and risk assessment.

Jia et al. develop SCOPE-C, a method to map open chromatin and associated chromatin loops from low-input samples. Applying it to the fetal cortex of humans, macaques, and mice, they show that human excitatory neurons form extended enhancer-promoter networks, enriched with human-biased enhancers and neurodevelopmental disorder SNPs, compared with those of other species.

Zan et al. have identified a neuroglial microcircuit within the central amygdala modulating anxiety symptoms comorbid with chronic pain through astrocytes. They find that pain induces dynorphin release by activating the CeLPdyn-CeM microcircuit. Dynorphin activates astrocytes by acting on kappa receptors to increase CeM neuron excitability by releasing gliotransmitter.

Ye, Shelton, et al. describe a silicon probe with ultra-high site density for recording neural activity in the brain. Higher site density improves the quality and yield of detected neurons. These probes robustly detect extracellular fields with small spatial extents, including axons, across species and brain regions. In addition, these probes improve classification of neuronal cell types.

Qin et al. reveal the spatiotemporal dynamics, clonality, and transcriptomic characteristics of SCI-associated Treg cells, identifying their crucial role in SCI functional recovery. Mechanistically, microglia act as essential MHC II antigen-presenting cells that sustain neuroprotective Treg cells, which in turn modulate microglial inflammation and cholesterol metabolism via CTLA-4 and Abcg1 upregulation.

(Neuron 113, 2760–2790; September 3, 2025)

Du et al. demonstrate that task data alone can map the detailed organization of within-individual brain networks. Applications include reanalysis of existing data, pooling of task and resting-state data to increase statistical power, and studies that solely acquire task data to simultaneously estimate brain networks and extract the evoked response.

Using advanced transcriptomic and physiological profiling, the authors identified deep-layer long-range GABAergic projection neurons as the most disrupted neuronal subtype and key contributor to brain dysfunction in the 15q13.3 neuropsychiatric mouse model. Late-onset impairments in these neurons disrupted sleep, which was rescued by chemogenetic inhibition, offering mechanistic insight and therapeutic potential.

(Neuron 112, 3585–3601.e1–e5; November 6, 2024)

Shafiei et al. introduce Reproducible Brain Charts (RBC), an open, reproducible developmental neuroimaging resource combining data from five large cohorts of youth. They provide harmonized psychiatric phenotypes, curated raw data, and uniformly processed derived imaging data. All data and processing pipelines are openly shared without a data use agreement.

Spinal cord stimulation (SCS) restores voluntary motor control after paralysis, but this experimental observation remains unexplained. In this study, Balaguer et al. show that residual brain inputs transform subthreshold, SCS-mediated excitatory postsynaptic potentials into action potentials, producing SCS-entrained motoneuron firing. The brain can regulate this entrainment, thereby mimicking volitional firing rate control.

Mapping mammalian neural circuits is limited by inefficient labeling and signal loss with depth. Zhong et al. develop LINCS, a chemical labeling toolkit for rapid, ultrabright neural visualization. This accessible pipeline provides robust and uniform connectivity analysis, from single neurons in cleared brains to circuits spanning the entire mouse body.

In this review, Khakh discusses the mechanisms, physiology, and pathophysiological relevance of astrocyte-neuron interactions across biological scales from molecules to whole organisms. By highlighting findings from the striatum, Khakh identifies insights of significance to other brain areas and summarizes key open questions and challenges.

Wang et al. demonstrate that hypothalamic GABAergic Crabp1 neurons promote energy expenditure by targeting multiple nuclei in mice. These neurons are activated by cold and exercise but suppressed by long photoperiod, linking environmental and physiological cues to metabolic homeostasis and offering a potential target for obesity intervention.

Ye et al. demonstrate a consistent developmental trajectory for variability in recurring brain state engagement (SEV) across four independent datasets (N > 3,000). SEV increases with age before plateauing in adolescence, with female participants reaching stabilization before male participants. SEV further predicts executive function (EF) in previously unseen individuals.

This review examines how chronic opioid use reshapes medial ventral tegmental area circuits, increasing sensitivity to aversive stimuli, amplifying negative affect, and reinforcing withdrawal-avoidance behaviors that drive opioid misuse. It also explores how chronic pain may exacerbate these effects through heightened aversive signaling, further increasing misuse risk.

This perspective examines sleep’s mechanism (“how”) and function (“why”). The motor theory posits that sleep is governed by distributed motor-control circuits; the catecholamine hypothesis identifies catecholamine inactivation as the unifying process underlying sleep’s restorative effects on metabolism, immunity, and cognition.

Huo et al. report that opioid-withdrawn mice prefer socializing with opioid-experienced peers, driven by heightened social motivation and mediated by a specific brain circuit, APIRCRH-BMA, activated by peer odor. This social homophily promotes relapse by strengthening addiction-related memories. Social support from non-addicted peers or blocking this pathway aids recovery.

In Croce et al. the discovery of a rare SNP in the Venezuelan HD kindreds that is associated with a delayed age of onset of up to 23 years reveals how preventing aberrant protein accumulation is protective not only against polyglutamine toxicity but also against α-synuclein- and tau-mediated toxicity.