搜索结果：Trends in neurosciences

Interoceptive signals inform the brain about physiological parameters, supporting bodily regulation-a process we refer to as the information mode of interoceptive signaling. Based on evidence in cardiac, respiratory, and gastric interoception, in rodents and humans, we argue for the existence of another mode: coordination. In the coordination mode of interoceptive signaling, the temporal patterns of interoceptive signals synchronize large-scale brain activity, independently of physiological state. The information and coordination modes might engage different pathways and brain structures. We further propose that the coordination mode underlies the single unified egocentric viewpoint from which people experience the world and themselves, a core yet unexplained feature of consciousness. The two modes would combine to generate interoceptive and emotional feelings. This hypothesis offers a novel account of some of the links between interoception and emotion in both health and psychiatric disorders.

Despite extensive research on hemispheric asymmetries, the mechanisms regulating lateralized brain functions are incompletely understood. Growing evidence suggests that lateralized neural circuits are side-specifically controlled, in part, by neuropeptides acting as neuromodulators, paracrine factors, and neurohormones. This review highlights evidence supporting this concept in the contexts of lateralized pain processing in the amygdala, control of auditory signaling, lateralized interoceptive signaling, and side-specific endocrine regulation. Our focus is primarily on rodent studies, with supporting data from humans and nonmammalian species, including turtles and nematodes. Left-right side-specific control may be rooted in a bipartite, lateralized organization of neuropeptide systems. Neuropeptides with asymmetric actions may act locally within specific brain regions or be coordinated across the neuraxis. These findings converge on a model in which neuropeptides enable lateralized control through interconnected mechanisms spanning gene expression, neural circuits, and behavioral outcomes.

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.

Atypical phonological processing is at the core of developmental dyslexia and is linked to aberrant tracking and analysis of auditory information in the cortex. Despite the importance of these mechanisms for speech processing and linguistic development, oral language comprehension in dyslexia remains largely intact. Recent findings suggest that dyslexia-linked atypical cortical processing patterns reflect both underlying deficits and compensatory strategies. This review synthesizes recent evidence linking atypical cortical tracking of auditory information in dyslexia, language development, and neurocognitive mechanisms of adaptive and resilient speech comprehension. We propose hemispheric rebalancing of linguistic analysis as a key compensatory mechanism in dyslexia, supported by interhemispheric connectivity within the distributed bilateral language network and greater reliance on lexico-semantic features during speech processing.

Monoaminergic neurotransmission has long been recognized as essential for the development, maintenance, and plasticity of the nervous system, with classical models defining serotonin, dopamine, and histamine as extracellular messengers acting through cell surface receptors. Broadening this view, emerging evidence reveals that biogenic amines also covalently modify proteins, a process termed 'monoaminylation', to directly influence intracellular signaling. The discovery of non-canonical monoamine signaling across subcellular compartments offers new insights into brain-body communication. Here, we review the evolving signaling landscape of protein monoaminylations and highlight new chemical-biological tools for probing their impact on neural development, plasticity, and disease.

Learning and memory arise from coordinated activity-dependent plasticity across neural circuits and brain regions. Astrocytes are increasingly recognized as active contributors to learning and memory via their roles in sensing, integrating, and responding to contextual information. Astrocytes modulate synaptic transmission, engage in circuit-specific signaling, and display context-dependent calcium dynamics that influence behavior. In this review, we focus on astrocyte functions across rodent models that display plasticity traditionally ascribed to neurons, including activity-dependent molecular and structural plasticity, circuit-level modulation, ensemble-like networks, and transcriptional, translational, proteomic, and epigenetic plasticity. Together, these findings redefine plasticity as an emergent property of the brain, regardless of cell type, in the context of learning and memory, and highlight the need for integrative, cell type-specific approaches to understanding complex behaviors.

Aging is the predominant risk factor for neurodegenerative diseases, yet the mechanisms linking biological aging to selective neuronal degeneration remain incompletely understood. Accumulating evidence indicates that aging progressively disrupts epigenetic regulation, manifested as increased epigenetic noise in DNA methylation, histone modifications, and chromatin accessibility, which undermines transcriptional precision and the stability of neuronal identity. Recent advances in single-cell and spatial epigenomics further suggest that these age-associated epigenetic alterations are not merely correlative but can actively shape neuronal vulnerability across brain regions and cell types. In this review, we synthesize emerging evidence showing how epigenetic noise contributes to selective neurodegeneration across Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease, and discuss emerging strategies aimed at stabilizing the aging neuronal epigenome.

This review summarizes experimental and clinical research advances in the field of sudden unexpected death in epilepsy (SUDEP) over the past 3 years. Novel animal models of SUDEP have been developed, highlighting the prevalence of peri-ictal respiratory dysfunction.The circumstances of SUDEP in genetic developmental and epileptic encephalopathies were found similar to those reported in more common epilepsies. Accordingly, most caregivers of patients with Dravet syndrome report using nocturnal monitoring devices and having averted critical incidents through such monitoring.Several prospective studies have identified novel SUDEP risk factors, including peri-ictal apnea, disrupted sleep homoeostasis, extratemporal epilepsies and elevated BMI. Retrospective analyses have additionally demonstrated associations between SUDEP and reduced polygenic risk scores for intelligence and longevityMultiple surveys highlight substantial gaps in SUDEP communication, with many people with epilepsy (PWE) and caregivers remaining insufficiently informed. This calls for action, given the accumulating evidence that optimizing seizure control is likely to reduce SUDEP risk. Recent advances in SUDEP research further support a central role for seizure-related respiratory dysfunction. Greater efforts are needed to improve communication with PWE and caregivers regarding SUDEP risk factors, and to promote optimized monitoring and therapeutic strategies.

Anxiety-related disorders are prevalent and can severely impact daily functioning, making the study of their underlying mechanisms a priority. Symptom provocation is an experimental approach enabling researchers to elicit and examine specific symptoms under controlled conditions in people affected by these disorders. This article provides an overview of symptom provocation techniques, their implementation, and their role in advancing research on anxiety-related disorders (including anxiety disorders, obsessive-compulsive disorder, and post-traumatic stress disorder). We outline key considerations for conducting high-quality symptom provocation studies, addressing study design and objectives, ethical considerations, experimenter training, study logistics, data validity, and opportunities for technological integration and collaboration. We provide guiding principles for obtaining more rigorous, reliable, and clinically meaningful findings to advance the current understanding of anxiety-related disorders.

Post-transcriptional regulation of AMPA-type ionotropic glutamate receptors (AMPARs) emerged in early vertebrates alongside a major expansion of AMPAR auxiliary subunits. Recent work shows that two key modifications-alternative splicing of the flip/flop cassette and Q/R site RNA editing-fine-tune channel gating and Ca2+ permeability, respectively, through interactions with two distinct auxiliary protein families: the transmembrane AMPA receptor regulatory proteins (TARPs) and the cornichons (CNIHs). I propose that these regulatory layers did not evolve independently but instead coalesced into an integrated system in which splicing, editing, and auxiliary proteins reciprocally shaped each other. This coordinated evolution maximized excitatory signaling diversity during vertebrate brain expansion, helping to explain why perturbations in any layer contribute to neurological disease.

Microglia are the brain's primary innate immune cells, which maintain neural homeostasis through surveillance, debris clearance, and synaptic remodeling. Dark microglia represent a distinct state of microglia that came into recent focus due to their excessive physical contact with synapses in contexts of pathological synapse loss, predominantly in neurodegenerative conditions, such as Alzheimer's disease. Dark microglia are identified by their unique ultrastructural features, exhibiting a dark, condensed appearance under electron microscopy. They display signs of cellular stress and appear to be engaged in synaptic pruning. Here, we review recent advances in understanding these intriguing cells in the mammalian brain, from new molecular insights into their origin to their emerging functional roles across the lifespan, in both health and disease.

Electroencephalography (EEG) microstates represent discrete topographic configurations persisting approximately 50-120 ms before transitioning to new patterns. These transient states provide unique insights into large-scale brain organization in health and disease, capturing reference-independent, zero-lag, synchronized networks at timescales matching cortical communication constraints. This review addresses critical methodological challenges in EEG microstates, including data-driven cluster optimization, template derivation strategies for group comparisons, and interpretive frameworks based on convergent evidence rather than premature functional consensus. Future advances will require transitioning from arbitrary conventions to optimization-based approaches, characterizing higher-order temporal dynamics, establishing multimodal integration, and building validation standards that prioritize convergent evidence. With methodological rigor, microstate analysis can advance our understanding of brain dynamics and their role in cognition, consciousness, and brain disorders.

The ingestion of foreign material-phagocytosis-is a fundamental feature shared across phyla, from single-celled ameba to more complex mammalian cells. Phagocytosis is a crucial process for maintaining homeostasis in body systems, including in the central nervous system (CNS). In this review, we first explore how phagocytic cells maintain CNS homeostasis by removing excess synapses, apoptotic cells, and debris. Next, we discuss the dual role of phagocytosis in CNS pathologies, including multiple sclerosis, aging, Alzheimer's disease, traumatic CNS injury, and ischemic stroke. During CNS pathology, phagocytosis aids debris removal and tissue repair, yet also contributes to damage through the engulfment of viable synapses and cells and via the release of cytotoxic mediators. Finally, we highlight current clinically relevant approaches and consider future directions for leveraging phagocytosis to enhance CNS repair and improve neurologic outcomes.

Cortical development is a tightly coordinated process driven by the self-renewal and differentiation of neural progenitors. Radial glia, the primary neuroectodermal progenitors of the cortex, generate diverse cortical cell types, in part through intermediate progenitors that amplify progenitor pools. Advances in single-cell profiling and lineage tracing have transformed the characterization and fate mapping of these intermediate progenitors. Notably, studies in mouse and human models have identified a new class of multipotent intermediate progenitors that generate cortical astrocytes, oligodendrocytes, and interneurons, broadening the classical view of glial-restricted progenitors. In this review, we synthesize emerging evidence for these intermediate progenitors, discuss the mechanisms underlying their specification, and propose an integrative framework for understanding their identity and role in cortical lineage specification.

Flight maneuvers in the fruit fly Drosophila have long served as a model for studying principles underlying visual information processing. Advances in genetic targeting of individual types of neurons for manipulation and recording, as well as the publication of the complete connectome, have greatly expanded our knowledge of how behavior is controlled by the fly's nervous system. In this review, I summarize recent findings on how visual information relevant to flight is transformed into a behavioral output, ranging from fast stabilizing reflex-like responses to longer-lasting goal-directed behaviors. I argue that flexibility in the processing of visual information and a hierarchical recruitment of different behavioral modules enable the control of this complex behavior with a comparatively small number of neurons.

Nervous system function is contingent on accurate neuronal connectivity patterns. A single neuron must often connect with multiple synaptic partners. Excitatory cortical projection neurons in the mammalian brain are a prime example of neurons whose axons innervate multiple distant target regions. This is made possible, in part, by interstitial axon branches that extend from axon shafts during development. The identification of molecular mechanisms that regulate interstitial axon branching in cortical projection neurons remains a major challenge. In this review, we summarize known stereotyped interstitial axon branching patterns in the mammalian brain and their spatiotemporal and molecular developmental cues. Taken together, these discoveries provide a foundation for understanding and identifying the molecular determinants that direct cortical connectivity during neural development.

Synaptic vesicle glycoprotein 2 (SV2) isoforms are crucial for synaptic function and neurotransmission. Although their precise physiological roles remain unclear, SV2 proteins serve as receptors for several botulinum neurotoxins (BoNTs) and are also the targets of anticonvulsants. Recent cryo-electron microscopy (cryo-EM) studies have greatly advanced our understanding of the structure and function of both SV2 proteins and BoNTs. The findings unveiled the molecular architectures of BoNTs, their receptors SV2A and SV2B, and how anticonvulsants bind to SV2A and how these interactions can be modulated allosterically. Additionally, the studies revealed a conserved binding mode in the interaction between BoNT/A and SV2 proteins, which involves significant conformational changes in the toxin. In this review, we will discuss these findings and their implications.

Brain-computer interfaces (BCIs) decode neural activity to enable direct communication with external devices. This process consists of three modules: signal acquisition, signal processing, and output translation. While invasive BCIs have demonstrated sophisticated and intuitive capabilities, their reliance on surgical implantation limits widespread use. Noninvasive BCIs, in contrast, are more broadly applicable but have traditionally been constrained by low spatial resolution and suboptimal signal quality. Emerging methodological advances are beginning to overcome these limitations. In this review, we examine recent progress in noninvasive BCIs, focusing on neuromodulation-paired BCIs for signal enhancement, deep neural network-based signal processing approaches, and expanded applications through robotic integration. Together, these parallel developments are driving the emergence of more robust, intuitive, and adaptive BCI systems for human use.

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.