Trends in Neurosciences最新文献

In a recent study, Spencer and colleagues demonstrated that high-frequency microsimulation of the globus pallidus internus (GPi) in individuals with Parkinson's disease induces long-term potentiation (LTP)-like effects in the inhibitory pathways, leading to transient improvements in bradykinesia that can persist beyond stimulation cessation. Their results highlight the potential of leveraging synaptic plasticity mechanisms in deep brain stimulation (DBS) to optimize therapy.

The brain constantly generates predictions based on one's knowledge of the world, as captured in memory. When these predictions are in error, our knowledge base must be revised to remain relevant. Here, we propose that this error-driven updating of memory depends largely on the interplay between the hippocampus and locus coeruleus (LC), during which the former conveys information about surprise to the latter, signaling the magnitude of prediction error. Small prediction errors promote editing of existing memories, whereas large prediction errors lead to the formation of new episodic memories. We suggest that this memory curation process is central to adaptive behavior, extending classical views on the contributions of the LC to cognition.

In a recent publication, Broix, Roy, and colleagues have shown that m⁶A controls local translation of the RNA-binding protein APC via YTHDF1, coupling RNA modification to β-actin mRNA local translation and axon growth. In addition, autism- and schizophrenia-associated METTL14 variants weaken YTHDF1-APC binding, reduce APC, and shorten axons, underscoring their involvement in neurodevelopmental disorders.

Growing evidence documents that the influence of sedentary behaviors on brain health is not universally beneficial or detrimental but rather context-dependent and nuanced. More specifically, recent findings suggest that mentally active sedentary behavior, such as video gaming, may benefit brain health, whereas mentally passive sedentary behavior, such as television viewing, may not convey such benefits. However, traditional classification approaches do not fully recognize the importance of content relevance. In this opinion article, we propose a neurobiological, dual-axis framework combining mental activation and content relevance to distinguish effects of specific sedentary behavior types on brain health-related outcomes. This refined sedentary behavior taxonomy may open novel perspectives to clarify mechanisms and the roles of key moderators (e.g., age and life context) in future brain health research for enhanced public health strategies and more personalized lifestyle recommendations.

Control of behavior is often explained in terms of a dichotomy, with distinct neural circuits underlying goal-directed and habitual control, yet accumulating evidence suggests these processes are deeply intertwined. We propose a novel anatomically informed cognitive framework, motivated by interacting corticobasal ganglia-thalamocortical loops as observed in different mammals. The framework shifts the perspective from a strict dichotomy toward a continuous, integrated network where behavior emerges dynamically from interacting circuits. Decisions within each loop contribute contextual information, which is integrated with goal-related signals in the basal ganglia input, building a network of dependencies. Loop-bypassing shortcuts facilitate habit formation. Striatal integration hubs may function analogously to attention mechanisms in Transformer neural networks, a parallel we explore to clarify how a variety of behaviors can emerge from an integrated network.

A recent study by Lindman and colleagues highlights a cell type-specific function of receptor-interacting kinase 3 (RIPK3) in astrocytes during neurotropic flavivirus infection. Despite a proinflammatory transcriptional profile, RIPK3 in astrocytes can attenuate neuroinflammation and reduce leucocyte infiltration through upregulation of Serpin clade A member 3N (SerpinA3N), protecting mice from excessive neuroinflammation and increasing overall survival.

Noxious heat sensation involves multiple molecular receptors that operate under complex regulatory mechanisms. In a recent study, Gao, Yan, and colleagues identified Copine-6 as a calcium-sensitive phospholipid-binding protein that promotes TRPM3 trafficking to the plasma membrane in thermal sensory neurons and thereby enhances noxious heat sensitivity in mice. These findings expand current understanding of the mechanisms regulating thermal sensation.

The integrated stress response (ISR) is an evolutionarily conserved signaling network that regulates protein synthesis in response to diverse cellular stressors to promote stress adaptation. The ISR also responds to physiological stimuli to modify the cellular proteome in an activity-dependent manner. Many common brain pathologies, including neurodegenerative and neurodevelopmental disorders, induce chronic cellular stress and subsequent ISR activation, which substantially contributes to disease progression. Importantly, various brain cell types exhibit disparate levels of sensitivity to cellular stress and differ in how the activation of the ISR influences their physiology. In this review, we highlight cell type-specific roles of the ISR in brain health and disease. We also discuss how therapeutically targeting the ISR in pathological states should account for the cell types being affected.

Nausea serves as a protective response against harmful ingested stimuli but can also be experienced as a discomforting aspect of various conditions. Recent insights have emerged regarding neural pathways and molecular mechanisms linked to this sensation. This often involves complex interactions of interoceptive neural pathways with the digestive, endocrine, and immune systems. This review summarizes recent findings using non-emetic (e.g., rodents) and emetic (e.g., ferrets, shrews, dogs) mammalian models to explore the molecular mechanisms of nausea, particularly in understudied malaise states. By investigating how nausea is triggered across different contexts, we aim to clarify the general sensory principles governing this response and to promote a shift in therapeutic research - from a top-down, observational paradigm to a bottom-up, mechanism-driven approach.

Neuronal death is a defining feature of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and motor neuron diseases, and is accordingly a priority drug target. Among the various cell death pathways, ferroptosis, a form of regulated necrosis driven by iron-dependent lipid peroxidation, has emerged as a prominent candidate underlying neurodegeneration. Despite its potential significance, putative triggers initiating lipid peroxidation cascades that lead to ferroptosis in neurodegenerative diseases remain poorly characterized. This poses significant challenges for developing targeted and disease-specific therapies. We review evidence of ferroptosis in neurodegenerative diseases and examine potential disease-relevant triggers of ferroptosis. We propose that ferroptosis, rather than being initiated by a single triggering event, emerges due to a cumulative erosion of anti-ferroptosis defense systems. This process is likely driven by context-dependent interplay between common hallmarks of neurodegenerative diseases, including neuroinflammation, protein aggregation, mitochondrial dysfunction, altered lipid metabolism, and iron accumulation.