Trends in Neurosciences最新文献

Oligodendrocyte lineage cells (OLCs), comprising oligodendrocyte precursor cells (OPCs) and oligodendrocytes, are pivotal in sculpting central nervous system (CNS) architecture and function. OPCs mature into oligodendrocytes, which enwrap axons with myelin sheaths that are critical for enhancing neural transmission. Notably, OLCs actively respond to neuronal activity, modulating neural circuit functions. Understanding neuron-OLC interactions is key to unraveling how OLCs contribute to CNS health and pathology. This review highlights insights from zebrafish and mouse models, revealing how synaptic and extrasynaptic pathways converge to shape spatiotemporal calcium (Ca²⁺) dynamics within OLCs. We explore how Ca²⁺ signal integration across spatial and temporal scales acts as a master regulator of OLC fate determination and myelin plasticity.

Bridging integrator 1 (BIN1) is a ubiquitously expressed protein that plays a critical role in endocytosis, trafficking and cytoskeletal dynamics. In 2010, BIN1 gene was reported as a major genetic risk factor for Alzheimer's disease (AD), which shifted the focus on its physiological and pathophysiological roles in the brain (at a time when data available were scarce). In this review, we discuss the multiple cerebral roles of BIN1, especially in regulating synaptic function, and the strong link between BIN1 and tau pathology, supported by recent evidence ranging from genetic and clinical/postmortem observations to molecular interactions.

Somatic mutations in genes regulating mechanistic target of rapamycin (mTOR) pathway signaling can cause epilepsy, autism, and cognitive dysfunction. Research has predominantly focused on mTOR regulation of excitatory neurons in these conditions; however, dysregulated mTOR signaling among interneurons may also be critical. In this review, we discuss clinical evidence for interneuron involvement, and potential mechanisms, known and hypothetical, by which interneurons might come to directly harbor pathogenic mutations. To understand how mTOR hyperactive interneurons might drive dysfunction, we review studies in which mTOR signaling has been selectively disrupted among interneurons and interneuron progenitors in mouse model systems. Complex cellular mosaicism and dual roles for mTOR (hyper)activation in mediating disease pathogenesis and homeostatic responses raise challenging questions for effective treatment of these disorders.

In a recent study, Dykstra and colleagues show that shortened TAR DNA Binding Protein 43 (sTDP-43) isoforms are generated as by-products of TDP-43 autoregulation. sTDP-43 levels are regulated through nonsense-mediated decay and proteasomal and autophagic degradation, and elicit toxicity through dominant negative effects on TDP-43 splicing activity. These results identify mechanisms contributing to sTDP-43 accumulation and toxicity in disease.

'Brain fog' is commonly reported in more than a dozen chronic diseases, but what is it? We review research across conditions which has characterised brain fog and evaluate its definitions and objective correlates. Brain fog has been used to refer to a variable set of overlapping symptoms implicating cognition, fatigue, and affect. It has been defined as a distinct symptom, a syndrome, or a nonspecific term. We consider the evidence that brain fog is a transdiagnostic entity with a common phenomenology and profile of objective cognitive deficits. We discuss where these commonalities arise and argue that linguistic ambiguity, shared cognitive impairments, and noncognitive factors are more likely than shared neurobiology. We suggest how future research might apply existing tools to disambiguate the phenomena that brain fog conflates.

Accurately measuring brain inflammation in Alzheimer's disease (AD) is crucial due to the role of inflammatory processes in neurodegeneration. In a recent study, Appleton, Finn, et al. used [¹¹C]ER176, a novel translocator protein 18 kDa (TSPO)-positron emission tomography (PET) tracer overcoming genotype-related binding issues, to show increased inflammation in early-onset AD, with patterns aligning more closely with tau pathology than amyloid deposition or atrophy.

In a recent study, Im, Shirahatti, and Isik used voxel-wise encoding modelling to show that cues to social interaction predict brain activity in children aged 3-12 years. Their findings have implications for understanding early social development, and their approach holds promise for investigating other domains of cognitive development.

Understanding how innate predispositions and learned experiences interact to shape behavior is a central question in systems neuroscience. Traditionally, innate behaviors, that is, those present without prior learning and governed by evolutionarily conserved neural circuits, have been studied separately from learned behaviors, which depend on experience and neural plasticity. This division has led to a compartmentalized view of behavior and neural circuit organization. Increasing evidence suggests that innate and learned behaviors are not independent, but rather deeply intertwined, with plasticity evident even in circuits classically considered 'innate'. In this opinion, we highlight examples across species that illustrate the dynamic interaction between these behavioral domains and discuss the implications for unifying theoretical and empirical frameworks. We argue that a more integrative approach, namely one that acknowledges the reciprocal influences of innate and learned processes, is essential for advancing our understanding of how neuronal activity drives complex behaviors.

The enteric nervous system (ENS), an elaborate network of neurons and glia woven through the gastrointestinal tract, is integral for digestive physiology and broader human health. Commensurate with its importance, ENS dysfunction is linked to a range of debilitating gastrointestinal disorders. MicroRNAs (miRNAs), with their pleiotropic roles in post-transcriptional gene regulation, serve as key developmental effectors within the ENS. Herein, we review the regulatory dynamics of miRNAs in ENS ontogeny, showcasing specific miRNAs implicated in both congenital and acquired enteric neuropathies, such as Hirschsprung's disease (HSCR), achalasia, intestinal neuronal dysplasia (IND), chronic intestinal pseudo-obstruction (CIPO), and slow transit constipation (STC). By delineating miRNA-mediated mechanisms in these diseases, we underscore their importance for ENS homeostasis and highlight their potential as therapeutic targets.

Neurobehavioural disturbances such as loss of motivation have profound effects on the lives of many people living with Parkinson's disease (PD), as well as other brain disorders. The field of decision-making neuroscience, underpinned by a plethora of work across species, provides an important framework within which to investigate apathy in clinical populations. Here we review how changes in a number of different processes underlying value-based decision making may lead to the common phenotype of apathy in PD. The application of computational models to probe both behaviour and neurophysiology show promise in elucidating these cognitive processes crucial for motivated behaviour. However, observations from the clinical management of PD demand an expanded view of this relationship, which we aim to delineate. Ultimately, effective treatment of apathy may depend on identifying the pattern in which decision making and related mechanisms have been disrupted in individuals living with PD.