Trends in Neurosciences最新文献

Rapid eye movement (REM) sleep is a unique state classically defined by brain activation and muscle paralysis. It is now recognized as a dynamic process involving coordinated oscillations and phasic behaviors, with substantial variations across development and species. Neural circuit studies have identified ever-expanding brain networks that regulate state generation and individual components of REM sleep. To account for this structured yet flexible nature, we propose a hierarchical circuit framework in which core REM sleep features are generated by brainstem nuclei, and adaptively tuned by hypothalamic, cortical, and neuromodulatory systems. From this component- and circuit-based perspective, we synthesize recent advances showing how theta oscillations and distributed forebrain circuits mediate REM sleep functions in memory, emotion, and cognition. We finally outline future research paths towards a more refined and integrative understanding of REM sleep.

Neurons are highly polarised and compartmentalised cells with organelles that are specialised to support their spatial and functional demands. This includes lysosomes, which are single-membrane-bound organelles enveloping acidic contents enriched with hydrolytic enzymes. While classically thought to be localised at the soma where they degrade waste, lysosomes have a range of dynamic nondegradative functions throughout neurons. Here, we review lysosomal dynamics and non-canonical functions in neurons, including axonal mRNA transport, mammalian target of rapamycin (mTOR) and Ca²⁺ signalling, neuronal remodelling, and interorganellar contact sites. We synthesise work across a range of model systems and species, providing insights from neurological diseases, where previous lysosomal research has focussed on proteostatic failure. This perspective highlights the need to better define lysosomal heterogeneity, compartmentalisation and specialisation in neurons.

Microglia are resident immune cells of the central nervous system (CNS) that dynamically adapt to their microenvironment to achieve multiple housekeeping roles. While ex vivo and in vitro models are instrumental tools to study microglial function, the slicing or culturing process inherently leads to markedly altered microglial phenotypes. Understanding the nature of these limitations and developing better ex vivo and in vitro models are crucial for enhancing the utility of these methods. In this review, we discuss recent developments in ex vivo and in vitro microglia models, from cell cultures to brain slices, focusing on the mechanisms that may need to be considered when using these tools and interpreting the obtained results. We suggest that limitations of ex vivo and in vitro models also provide opportunities to better understand the mechanisms driving microglial phenotype changes in various disease states.

In a recent article, Légaré and colleagues demonstrate that key mammalian brain network organizational features, which have been extensively mapped in human functional connectivity studies, are conserved in the tiny vertebrate brain of the larval zebrafish. Using whole-brain calcium imaging, single-cell reconstructions, and network analyses, the authors reveal how features from structural connectomes and genetic markers predict sensorimotor functional correlations.

Viral infections cause a wide range of neurocognitive disorders. However, the molecular mechanisms that give rise to acute and chronic cognitive deficits remain poorly understood. In this opinion article we review current knowledge on the close interactions between viruses and synapses from animal and human-based models, including how viral infections restructure synapses, disrupt synaptic transmission and neuromodulation, and interfere with synaptic plasticity, as well as how synapses contribute to viral dissemination. We further discuss how neuroimmune responses can both contribute to host defense and cause pathological damage to the nervous system that can lead to cognitive deficits. The emerging field of cognitive virology aims for expanded interdisciplinary studies to understand the molecular mechanisms by which viral infections lead to cognitive dysfunction.

The study of foraging is central to a renewed interest in naturalistic behavior in neuroscience. Applying a foraging framework grounded in behavioral ecology has enabled probing of the mechanisms underlying cognitive processes such as decision-making within a more ecological context. Yet, foraging also involves myriad other aspects, including navigation of complex environments, sensory processing, and social interactions. Here, we first provide a brief overview of the neuroscience of foraging decisions, and then combine insights from behavioral ecology and neuroscience to review the role of these additional dimensions of foraging. We conclude by highlighting four opportunities for the continued development of foraging as an ethological framework for neuroscience: integrating normative and implementation-level models, developing new tools, enabling cross-species comparisons, and fostering interdisciplinary collaboration.

Mesenchymal stromal cells (MSCs) hold significant therapeutic potential, but their clinical application is often hindered by limitations such as donor variability. MSC-derived extracellular vesicles (EVs) present a promising alternative, offering comparable or superior therapeutic effects while overcoming some of these challenges. MSC-EVs exhibit strong anti-inflammatory and immunomodulatory properties, which could be leveraged in neurodegenerative diseases given the central role of neuroinflammation in these conditions. Additionally, MSC-EVs can be engineered for targeted drug delivery, enhancing their clinical utility. In this review we highlight the dual role of MSC-EVs as immunomodulators and drug carriers in neurodegenerative disorders. We discuss the current challenges, and outline strategies for clinical translation. Future advances in understanding MSC-EVs and their mechanisms of action could support their development into effective therapies for neurodegenerative diseases.

The organisation of thalamocortical networks follows a conserved structure. Traditionally, these are divided into primary sensory systems that receive subcortical sensory signals, and higher-order systems that are driven predominantly by cortical activity. The rodent head-direction system - the 'neural compass' and a key input to the hippocampal formation - encodes orientation in the horizontal plane through a thalamocortical loop that links the anterodorsal thalamic nucleus and the postsubiculum (dorsal presubiculum). We argue that this circuit shares several hallmark features with canonical primary sensory systems, including a driver thalamic input, specific laminar targeting, and receptive field transformations. Drawing on recent anatomical and physiological studies in rodents, we propose that the postsubiculum functions as a primary cortex for the head-direction signal.

Circadian regulation is multilayered and hierarchical, enabling organisms to anticipate and adapt to daily environmental changes driven by the Earth's rotation. The classical transcriptional-translational feedback loop (TTFL) remains a foundational model, although recent studies have refined its mechanisms and exposed limitations. The discovery of RUVBL2 - an ancient core clock component conserved across eukaryotes - emphasizes the potential universality of fundamental timekeeping processes. In mammals, intercellular coupling enables the generation of precise and robust circadian rhythms in both metabolic and electrical activity within the central pacemaker, the suprachiasmatic nucleus (SCN). The SCN receives external cues and coordinates systemic physiology to adjust to daily environmental changes. This review provides an updated perspective on mechanisms underlying the generation of mammalian circadian rhythms from molecular to neural and circuit levels.

Synapses are traditionally defined by the presence of presynaptic vesicle pools and postsynaptic densities. Dopaminergic neurons, however, frequently form bouton-like structures that lack these conventional postsynaptic specializations. Recently, high-resolution imaging techniques such as electron microscopy and correlative light and electron microscopy, along with nanosensors and in vitro models, have revealed the molecular identities and spatial organization of distinct vesicle pools in dopaminergic terminals. In this review, we discuss how recent findings have reshaped current understanding of dopamine vesicles, revealing a structural continuum that includes non-classical architectures. We highlight emerging concepts such as dopamine hub synapses and vesicle heterogeneity in dopaminergic terminals. Finally, we examine how dysfunction in Parkinson's disease-associated proteins affects synaptic integrity and predisposes dopaminergic neurons to selective vulnerability.