The brain must learn to associate sensory experiences with delayed physiological consequences in order to generate adaptive behavior. The insular cortex is uniquely positioned to support this function, integrating gustatory, visceral, immune, pain, affective, and metabolic information into representations of bodily states. In this review, we examine evidence, primarily from mouse and rat studies and with reference to human work, that insular circuits couple external cues to predicted bodily states. We focus on conditioned taste aversion and conditioned immune responses as complementary models of this computation, in which initially neutral sensory stimuli acquire the ability to evoke learned behavioral or physiological responses despite substantial temporal delays. We discuss how anterior and posterior insular circuits, projection-specific plasticity, inhibitory gating, and molecular mechanisms contribute to the encoding, updating, and retrieval of these associations. This framework positions the insula as a state-dependent hub, generating and regulating learned predictions about the body's future physiological states and needs.

Somatic expansion of the HTT CAG repeat is a key feature of Huntington's disease (HD) pathogenesis. Mismatch repair (MMR) enzymes drive this process through erroneous DNA repair, with variants in MMR genes modifying the onset and progression of disease features. Cell-type-specific CAG repeat sizing recently confirmed that elevated somatic expansion underlies the selective vulnerability of HD medium spiny neurons, with expansion beyond certain CAG thresholds associated with distinct stages of cellular pathogenesis. In this review, we synthesise insights from post-mortem brain tissue, cell systems, and mouse models, detailing key CAG repeat-length-dependent changes. In addition, we critically evaluate the MMR proteins MSH3, MLH3, and PMS1 as therapeutic targets for slowing somatic expansion and outline key safety considerations for emerging MMR-modulating approaches.

The ventral tegmental area (VTA) has traditionally been framed as a hub for motivation and positive reinforcement learning. However, growing evidence reveals that the VTA is also deeply embedded in defensive computations. Across glutamatergic, GABAergic, and dopaminergic populations, VTA neurons respond to aversive stimuli and can initiate innate defensive behaviors when manipulated. Here, we synthesize recent advances showing that VTA circuits detect threats, encode aversive salience, and orchestrate responses ranging from freezing and risk assessment to escape and defensive aggression. By integrating findings across cell types and circuits, we propose that the VTA functions as a dynamic threat-computation hub that maps threat imminence onto adaptive action policies. Stress-induced plasticity within VTA microcircuits may recalibrate defensive thresholds, offering a mechanistic bridge to anxiety disorders.

Depression is marked by anhedonia, social withdrawal, and a diminished capacity to learn from positive experiences-features that can be framed within predictive processing. Here, we review findings from human electroencephalography (EEG) that, owing to its temporal resolution, can illuminate the moment-to-moment dynamics of inference in depression. Across evoked, oscillatory, and aperiodic measures, incoming information appears to be registered yet may carry insufficient precision to revise higher-level beliefs about the self and the world. This imbalance may favour model maintenance over flexibility, with rumination as one possible subjective correlate of relative state stability. Together, these findings motivate inference phenotypes as a complementary lens on depression and yield testable predictions for EEG-guided stratification and mechanistically targeted intervention.

Neuroscience development in low- and middle-income countries is often constrained by multiple factors, including fragmented training, funding gaps, and limited infrastructure. However, the growth of neuroscience in Ghana has shown that professional coordination, training partnerships, and community-led initiatives can collectively build sustainable neuroscience ecosystems, offering transferable lessons for comparable contexts.

Unlike chemistry, which has the periodic table for abbreviations of the elements, neuroscience does not have agreed-upon abbreviations, even when neuroanatomical terminology is agreed upon. Neuroscientists at times mint abbreviations with little reference to what others do, resulting in parochial and haphazard schemes that clash when the entire central nervous system (CNS) is considered. In this article, we present the rationale for a unified, non-conflicting system of terms and abbreviations that spans species and development, covering CNS nuclei, tracts, nerves, and blood vessels, as well as related features of the peripheral nervous system and skull. Inspired by the logic of the periodic table, our rules generate concise, recognizable abbreviations, with homologous structures sharing the same term and abbreviation across species. Our associated online resource provides a list of over 3300 terms and abbreviations for humans, monkeys, rodents, and birds, designed to improve clarity in diagrams, text, and oral communication.

Neurogenesis requires precise coordination of gene expression, a process governed by the Polycomb (PcG) and Trithorax (TrxG) group proteins. In this review, we discuss how these proteins balance stem cell maintenance with neuronal differentiation and how the disruption of these processes may contribute to neurodevelopmental disorders and pediatric brain tumors. Recent studies have uncovered how PcG-TrxG dynamics and poised/bivalent chromatin states regulate developmental timing and lineage choice. Dysregulation of these epigenetic dynamics perturbs neuronal maturation and can drive aberrant developmental programs in pediatric brain disorders. These insights reveal how PcG-TrxG imbalance alters developmental trajectories and links chromatin dysregulation to disease. These epigenetic pathways are promising therapeutic targets for neurodevelopmental disorders and pediatric brain tumors.

Basal ganglia-cortical interactions are critical for goal-directed behavior. Sun et al. recently demonstrated a novel mechanism by which the striatum may impact the cortex via basal forebrain cholinergic neurons. These neurons are activated by D1 dopamine receptor-regulated striatal output through substance P release, which may increase arousal and attention and modulate other functions.

Although mammalian brains share a common structural plan, expanded neocortices contain specialized neuron types absent from smaller brains. Using human neurosurgical tissue, Ke and colleagues combined multimodal analyses to establish spindle neurons as a molecularly distinct and functionally specialized cortical cell population. Their findings highlight how brain evolution increases circuit complexity beyond simply adding neurons.

The glymphatic system is a brain-wide perivascular network hypothesized to facilitate the clearance of waste products that accumulate during normal brain activity, including neurotoxic proteins implicated in neurodegenerative diseases. Emerging evidence suggests that exercise may modulate glymphatic function, offering a potential mechanism to help explain the neuroprotective effects of exercise. In this review, we synthesize evidence from animal models and humans on the organization and regulation of the glymphatic system, examine its vulnerability to aging and neurodegenerative pathology, and discuss the potential roles of exercise in enhancing its function. We propose that the convergence between known regulators of glymphatic function and the physiological adaptations to exercise provides a mechanistic framework linking physical activity to glymphatic integrity and brain resilience.

Laughter is a universal social signal and a defining clinical sign of various neurological disorders. Yet, its neural orchestration remains elusive, due in part to the challenge of reproducing its spontaneous nature in the laboratory. In this review, we showcase how recent invasive investigations-from direct electrical stimulation to intracranial recordings-unveil the underlying circuitry. We propose a dual-system framework: an evolutionarily ancient cingulo-temporal network that acts as the gateway for spontaneous, involuntary outbursts; and a lateral motor-opercular system that co-opts speech-production networks for volitional, conversational laughter. This neuroethological perspective reveals how parallel cortico-subcortical pathways drive laughter as both a primal affective signal and a sophisticated communicative tool, offering a new roadmap for understanding human social bonding and its clinical disruptions.

The intestine contains a dense intrinsic nervous system that is closely integrated with local immune cells to coordinate motility, barrier defense, and tissue repair. Recent studies, primarily in mice and supported by emerging human evidence, have identified diverse enteric neuroimmune pathways through which enteric neurons shape immune cell responses, while immune cells, in turn, influence neuronal survival and function across distinct intestinal compartments. These bidirectional interactions are increasingly implicated in intestinal disorders, including Hirschsprung's disease, irritable bowel syndrome, inflammatory bowel disease, and infection-induced dysmotility. In this review, we summarize the anatomical basis and principal mechanisms of enteric neuroimmune communication, highlight recent advances in the field, and discuss key unresolved questions and future directions.

N-methyl-D-aspartate receptors (NMDARs) are essential for brain development, memory processes, and cognition. They primarily act as coincidence detectors at the synapse, integrating presynaptic glutamate release and postsynaptic membrane depolarization to open the channel gate. This allows the influx of cations (mainly calcium) into the postsynaptic neuron and triggers downstream signaling for synaptic plasticity. These receptors exhibit significant diversity in atomic structure, subunit composition, pharmacological properties, and biophysical characteristics. Advances in cryo-electron microscopy (cryo-EM) imaging have unlocked the structures of most recombinant NMDAR subtypes, providing a framework to understand their gating and pharmacological diversity. Furthermore, the ability to extract native NMDARs from rodent brain now positions the field to uncover their unique stoichiometry, assembly, and physiology in vivo. This review presents a synthesis of the emerging understanding of NMDAR physiological diversity and subtype-selective negative and positive allosteric modulation at atomic resolution, and it discusses potential directions for designing therapeutics based on these insights.

The globus pallidus externus (GPe) is a central nucleus in the basal ganglia. Although traditionally defined as a component of the basal ganglia's motor circuit, converging evidence from humans, rodents, and non-human primates has established the GPe as a key contributor to the cognitive control of behavior. In this role, the GPe dynamically regulates goal-directed behavior in response to changing environmental demands. In this review, we highlight recent studies demonstrating that the GPe encodes cue and action values, supports behavioral flexibility, and modulates attention, behavioral inhibition, and habit formation. The picture that emerges is of a nucleus that aligns behavior to internal goals by constraining, updating, and optimizing ongoing actions.

In a recent study, Chikamoto and colleagues challenged the view that velocity tuning of axons associated with Pacinian corpuscles arises from interactions between the axon terminal and the surrounding lamellar cells. Instead, their investigations of duck tactile corpuscles and mouse Piezo2 suggest that this feature arises from Piezo2 properties.