Berdugo-Vega et al. combine partial reprogramming and engram technologies to achieve molecular rejuvenation of learning-associated neuronal ensembles. Engram reprogramming counteracts molecular, cellular, and electrophysiological signs of aging and disease and is associated with behavioral improvements that are consistent with a rejuvenation of learning and memory capacities.

Cruddas et al. reviewed how core concepts from wave physics relate to cortical wave physiology and psychology. They examined how cortical waves emerge, how they facilitate coordinated, hierarchical, and counterstream dynamics, and how they encode perceptual and behavioral signals.

Novelty can directly impact valuation of future outcomes, affecting how we choose among rewards such as food or money. This is the case even when novelty is objectively valueless. Here, Ogasawara et al. shed light on how a temporal-orbitofrontal cortical circuit integrates novelty and physical reward to regulate decision-making.

Labouré et al. investigate the honeybee GABAA receptor, a protein targeted by many insecticides, using structural biology. The authors map out three specific allosteric binding sites on the receptor’s structure. One of those sites is a previously unknown allosteric site in the transmembrane domain.

Fenstermacher et al. map the structure and activity of spinal-projecting serotonergic neurons and show that 5-HT populations are engaged in a context-dependent manner during locomotion. Activation of ventrally projecting 5-HT neurons enhances the speed and endurance of ongoing locomotion, revealing serotonergic neurons can potentiate motor output over extended time scales.

Battista et al. use biologically plausible RNNs to uncover the circuit mechanisms of economic choice. They propose a two-stage framework where feedforward inputs compute offer values and recurrent inhibition drives comparison. This architecture explains how the brain generalizes preferences and multitasks using compositional neural codes, offering a unified theory of decision-making.

Liu et al. demonstrate that expanded C9orf72 G4C2 repeat RNAs bind gene promoters across the genome and form HQ structures with DNA. These structures obstruct key transcription machinery, repress gene expression, and heighten neuronal vulnerability, providing mechanistic insights into neurodegeneration in ALS and FTD.

Short-term plasticity (STP) filters synaptic inputs across rapid timescales. Nowacka et al. show that postsynaptic AMPAR desensitization and diffusion-trapping, shaped by auxiliary subunits and activity-dependent signaling, generate synapse-specific gain control. By broadening temporal filtering and adjusting short-term depression, receptor mobility emerges as a central regulator of circuit information processing.

Acute concurrent stresses provoke lasting, sex-dependent memory problems. Hokenson, Rodríguez-Acevedo, et al. find that high hippocampal estrogen levels in mice generate permissive chromatin states, allowing both adaptive plasticity and vulnerability to acute concurrent stresses. Stress vulnerability involves estrogen receptor (ER)α in males and ERβ in females.

Hu et al. show that the dentate gyrus engram comprises two neuronal ensembles: one supports remembering, and the other promotes forgetting. By shifting the balance between these ensembles via Rac1 signaling, the brain flexibly controls recall. Dysfunctions of the forgetting ensemble contribute to memory abnormalities in models of Alzheimer’s disease and autism.

Liu et al. propose the theoretical framework “granular motivational interaction orchestrates real-time behavioral choice,” exploring the dynamic interactions of granular motivational states in the feeding process, their neural bases, disrupting factors, and implications for understanding intelligence and psychiatric disorders.

Using mouse models, Zheng et al. show that social engagement promotes both innate and experience-dependent exploration. Dopaminergic neurons in the ventral tegmental area (VTA) encode risk assessment and exploratory motivation through firing pattern-biased DA transmission, thereby shaping exploration decisions via competing VTADA pathways that converge onto basolateral amygdala neurons.

Li et al. present a microLED-based mesoscale optogenetic system for centimeter-scale, million-pixel primate cortical stimulation. Optogenetically evoked saccades with accurate retinotopic organization remain stable for over a year, demonstrating precise, robust, and durable neuromodulation and charting a path toward next-generation optical brain-computer interfaces and visual prostheses.

Opioid responses differ across individuals. Runt-related transcription factor 1 (Runx1) modulates the microglial transcriptome, influencing opioid analgesia and withdrawal. RUNX1 variants may underlie inter-individual differences in opioid responses, guiding personalized strategies to optimize opioid pain management and minimize adverse outcomes.

Wang et al. reveal how nerve injury causes mechanical allodynia. It triggers endocannabinoid release, which disables the spinal Gly-PKCγ “allodynia gate” by disrupting inhibitory control. They develop a peptide that reverses this process, offering a promising strategy to alleviate chronic pain.

Crosstalk between the nervous and immune systems is imperative to maintain homeostasis, and disruptions to this balance can drive pathology. In this review, Kothari and Dong discuss neuroimmune mechanisms that regulate itch, with an emphasis on pruritic diseases and therapies.

Weinreb et al. reveal a hierarchy of timescales in mouse behavior, including low-level syllables and high-level behavioral states. States and syllables are encoded in different brain areas. Prefrontal encoding of behavioral states identifies principles common to both structured tasks and spontaneous behavior.

Transcranial focused ultrasound is emerging as a possible novel therapeutic tool for neurological and psychiatric disorders. This review covers three promising applications of this technology in human brain disorders based on high-intensity focused ultrasound (HIFU) and low-intensity focused ultrasound (LIFU).

Zolnik et al. propose that the long-overlooked neocortical layer 6b (L6b) supports a key circuit for attention and related cognitive functions. L6b integrates neuromodulatory and cortical feedback to trigger, sustain, and precisely control higher-order thalamocortical loops needed for attentive processing.

Salvador, Golynker, et al. discuss anatomical and functional principles of intestinal interoception. They explore how environmental factors impact interoceptive signaling, how interoceptive dysfunction contributes to disease pathogenesis, and how molecular enhancement of interoceptive function may restore organismal homeostasis.

Casto et al. systematically examine language-responsive regions of the cerebellum with precision fMRI. They find one region that closely resembles the neocortical language network in its selectivity for language and response to linguistic manipulations. They also find three mixed-selective regions that respond to language but also to non-linguistic inputs.

Ning et al. show that macaque prefrontal neurons encode remembered spatial locations along with uncertainty and combine them with cues, such as trial history and arousal, to generate a meta-working-memory signal guiding opt-out decisions. The findings reveal how the prefrontal cortex integrates multiple components for metacognitive judgments of working memory.