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Neural Circuits of Fear and Anxiety: Insights from a Neuroethological Perspective. 恐惧和焦虑的神经回路:从神经行为学角度的见解。
IF 5.3 2区 医学 Q1 PHYSIOLOGY Pub Date : 2025-05-01 Epub Date: 2024-12-11 DOI: 10.1152/physiol.00042.2024
Fernando Falkenburger Melleu, Newton Sabino Canteras

The predatory imminence continuum (PIC) of antipredator defensive behavior has been a helpful strategy for modeling anxiety and fear-related disorders in nonclinical research. The PIC is divided into three different sequential stages that reflect defensive behavioral strategy in response to predatory imminence. However, the PIC was experimentally addressed with a series of shock-based fear conditioning experiments rather than predatory threats. In this article, we consider the PIC in a more naturalistic behavioral setting, focusing on analyzing the neural systems of animals responding to terrestrial and aerial predators. Of relevance, there is a sequential engagement of the distinct neural circuits along each phase of the PIC. In the preencounter phase, prefrontal cortical networks are particularly involved in planning and organizing behavioral responses to ambiguous threats. As the predatory cues or the real predator is detected, there is an engagement of amygdalar and hippocampal > hypothalamic pathways in conjunction with the periaqueductal gray, which organize fear responses. This dynamic particularly reveals how specific neural circuits are set into action to subserve distinct defensive responses. Moreover, we further explore the neural circuits governing other fearful situations outside the context of the PIC, including agonistic social encounters and interoceptive challenges. This analysis reveals an interesting overlap between the neural systems responding to these threats and those involved in response to predatory threats. The present review clarifies how defensive circuits respond to natural threats and provides a more realistic view of the neural systems underlying anxiety and fear responses.

在非临床研究中,反捕食者防御行为的掠食性迫在眉睫连续统(PIC)已成为焦虑和恐惧相关障碍建模的有益策略。PIC分为三个不同的顺序阶段,反映了对掠夺性迫近的防御行为策略。然而,PIC是通过一系列基于冲击的恐惧条件反射实验而不是掠夺性威胁来解决的。在这项研究中,我们将在更自然的行为环境中考虑PIC,重点分析动物对陆地和空中捕食者的神经系统反应。相关的是,在PIC的每个阶段有不同的神经回路的顺序参与。在相遇前阶段,前额皮质网络特别参与计划和组织对模糊威胁的行为反应。当发现捕食线索或真正的捕食者时,扁桃体和海马>下丘脑通路与导水管周围灰质结合在一起,组织恐惧反应。这种动态特别揭示了特定的神经回路是如何开始行动的,以支持不同的防御反应。此外,我们进一步探索了在PIC背景之外控制其他恐惧情境的神经回路,包括激烈的社会遭遇和内感受性挑战。这项分析揭示了对这些威胁做出反应的神经系统和对掠夺性威胁做出反应的神经系统之间有趣的重叠。目前的综述阐明了防御回路如何对自然威胁作出反应,并提供了一个更现实的观点,即焦虑和恐惧反应背后的神经系统。
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引用次数: 0
Transforming Physiology and Healthcare through Foundation Models. 通过基础模型转变生理学和医疗保健。
IF 5.3 2区 医学 Q1 PHYSIOLOGY Pub Date : 2025-05-01 Epub Date: 2025-01-20 DOI: 10.1152/physiol.00048.2024
Ryan C Godwin, Avery Tung, Dan E Berkowitz, Ryan L Melvin

Recent developments in artificial intelligence (AI) may significantly alter physiological research and healthcare delivery. Whereas AI applications in medicine have historically been trained for specific tasks, recent technological advances have produced models trained on more diverse datasets with much higher parameter counts. These new, "foundation" models raise the possibility that more flexible AI tools can be applied to a wider set of healthcare tasks than in the past. This review describes how these newer models differ from conventional task-specific AI, which relies heavily on focused datasets and narrow, specific applications. By examining the integration of AI into diagnostic tools, personalized treatment strategies, biomedical research, and healthcare administration, we highlight how these newer models are revolutionizing predictive healthcare analytics and operational workflows. In addition, we address ethical and practical considerations associated with the use of foundation models by highlighting emerging trends, calling for changes to existing guidelines, and emphasizing the importance of aligning AI with clinical goals to ensure its responsible and effective use.

人工智能(AI)的最新发展可能会显著改变生理学研究和医疗保健服务。虽然医学领域的人工智能应用历来都是针对特定任务进行训练,但最近的技术进步已经产生了基于更多样化的数据集训练的模型,这些数据集具有更高的参数计数。这些新的“基础”模型提出了一种可能性,即比过去更灵活的人工智能工具可以应用于更广泛的医疗保健任务。这篇综述描述了这些新模型与传统的特定任务人工智能的不同之处,后者严重依赖于集中的数据集和狭窄的特定应用。通过研究人工智能与诊断工具、个性化治疗策略、生物医学研究和医疗保健管理的集成,我们强调了这些新模型如何彻底改变预测医疗保健分析和运营工作流程。此外,我们通过强调新兴趋势,呼吁改变现有指南,并强调将人工智能与临床目标保持一致以确保其负责任和有效使用的重要性,解决与基础模型使用相关的伦理和实际考虑。
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引用次数: 0
Regulation of Cardiac Function by the Autonomic Nervous System. 自律神经系统对心脏功能的调节。
IF 5.3 2区 医学 Q1 PHYSIOLOGY Pub Date : 2025-05-01 Epub Date: 2024-11-25 DOI: 10.1152/physiol.00018.2024
Omar A Hafez, Rui B Chang

The autonomic nervous system is critical for regulating cardiovascular physiology. The neurocardiac axis encompasses multiple levels of control, including the motor circuits of the sympathetic and parasympathetic nervous systems, sensory neurons that contribute to cardiac reflexes, and the intrinsic cardiac nervous system that provides localized sensing and regulation of the heart. Disruption of these systems can lead to significant clinical conditions. Recent advances have enhanced our understanding of the autonomic control of the heart, detailing the specific neuronal populations involved and their physiologic roles. In this review, we discuss this research at each level of the neurocardiac axis. We conclude by discussing the clinical field of neurocardiology and attempts to translate this new understanding of neurocardiac physiology to the clinic. We highlight the contributions of autonomic dysfunction in prevalent cardiovascular diseases and assess the current status of novel neuroscience-based treatment approaches.

自律神经系统对于调节心血管生理至关重要。心脏神经轴包含多个控制层次,包括交感神经系统和副交感神经系统的运动回路、促进心脏反射的感觉神经元以及提供心脏局部感应和调节的心脏固有神经系统。这些系统受到破坏会导致严重的临床症状。最近的研究进展增进了我们对心脏自主神经控制的了解,详细说明了其中涉及的特定神经元群及其生理作用。在这篇综述中,我们将讨论神经-心脏轴各层次的研究。最后,我们将讨论神经心脏病学的临床领域,以及将对神经心脏病生理学的这一新认识应用于临床的尝试。我们强调了自律神经功能紊乱在心血管疾病中的作用,并评估了基于神经科学的新型治疗方法的现状。
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引用次数: 0
Targeting Sleep Physiology to Modulate Glymphatic Brain Clearance. 以睡眠生理为目标,调节大脑甘油清除。
IF 5.3 2区 医学 Q1 PHYSIOLOGY Pub Date : 2025-05-01 Epub Date: 2024-11-27 DOI: 10.1152/physiol.00019.2024
Timo van Hattem, Lieuwe Verkaar, Elena Krugliakova, Nico Adelhöfer, Marcel Zeising, Wilhelmus H I M Drinkenburg, Jurgen A H R Claassen, Róbert Bódizs, Martin Dresler, Yevgenia Rosenblum

Sleep has been postulated to play an important role in the removal of potentially neurotoxic molecules, such as amyloid-β, from the brain via the glymphatic system. Disturbed sleep, on the other hand, may contribute to the accumulation of neurotoxins in brain tissue, eventually leading to neuronal death. A bidirectional relationship has been proposed between impaired sleep and neurodegenerative processes, which start years before the onset of clinical symptoms associated with conditions like Alzheimer's and Parkinson's diseases. Given the heavy burden these conditions place on society, it is imperative to develop interventions that promote efficient brain clearance, thereby potentially aiding in the prevention or slowing of neurodegeneration. In this review, we explore whether the metabolic clearance function of sleep can be enhanced through sensory (e.g., auditory, vestibular) or transcranial (e.g., magnetic, ultrasound, infrared light) stimulation, as well as pharmacological (e.g., antiepileptics) and behavioral (e.g., sleeping position, physical exercise, cognitive intervention) modulation of sleep physiology. A particular focus is placed on strategies to enhance slow-wave activity during nonrapid eye movement sleep as a driver of glymphatic brain clearance. Overall, this review provides a comprehensive overview on the potential preventative and therapeutic applications of sleep interventions in combating neurodegeneration, cognitive decline, and dementia.

据推测,睡眠在通过淋巴系统将淀粉样蛋白-β等潜在神经毒性分子排出大脑方面发挥着重要作用。另一方面,睡眠紊乱可能导致神经毒素在脑组织中积累,最终导致神经元死亡。有人提出,睡眠障碍与神经退行性病变过程之间存在双向关系,而神经退行性病变过程在阿尔茨海默氏症和帕金森氏症等疾病的临床症状出现前数年就已开始。鉴于这些疾病给社会带来的沉重负担,当务之急是制定干预措施,促进大脑的有效清除,从而有可能帮助预防或减缓神经退行性病变。在这篇综述中,我们将探讨是否可以通过感官(如听觉、前庭)或经颅(如磁力、超声波、红外线)刺激,以及药物(如抗癫痫药)和行为(如睡姿、体育锻炼、认知干预)调节睡眠生理学来增强睡眠的代谢清除功能。其中特别强调了在非快速眼动睡眠中加强慢波活动的策略,因为慢波活动是大脑甘油清除的驱动力。总之,这篇综述全面概述了睡眠干预在预防和治疗神经退化、认知功能衰退和痴呆症方面的潜在应用。
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引用次数: 0
Sweat the Small Stuff. 为小事操心。
IF 5.3 2区 医学 Q1 PHYSIOLOGY Pub Date : 2025-05-01 Epub Date: 2024-12-24 DOI: 10.1152/physiol.00057.2024
Kyle J Mahoney
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引用次数: 0
Off to the Races: How the Thoroughbred Is Helping Us Understand Skeletal Muscle. 比赛开始:纯种马如何帮助我们理解骨骼肌。
IF 5.3 2区 医学 Q1 PHYSIOLOGY Pub Date : 2025-05-01 Epub Date: 2024-12-26 DOI: 10.1152/physiol.00062.2024
Madison R Barshick
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引用次数: 0
Histone Deacetylases in Metabolism: the Known and the Unexplored. 代谢中的组蛋白去乙酰化酶:已知与未知。
IF 5.3 2区 医学 Q1 PHYSIOLOGY Pub Date : 2025-05-01 Epub Date: 2024-10-29 DOI: 10.1152/physiol.00044.2024
Somaya Y Ibrahim, Jayden Carter, Rushita A Bagchi

Histone deacetylases (HDACs) are enzymes that catalyze the removal of acetyl groups from key lysine residues on histone and nonhistone proteins and thereby regulate gene transcription. They have been implicated in several biological processes in both healthy and pathological settings. This review discusses the role of HDACs in multiple metabolically active tissues and highlights their contribution to the pathogenesis of tissue-specific maladaptation and diseases. We also summarize the current knowledge gaps and potential ways to address them in future studies.

组蛋白去乙酰化酶(HDACs)是一种催化去除组蛋白和非组蛋白上关键赖氨酸残基上乙酰基从而调节基因转录的酶。它们与健康和病理环境中的多个生物过程都有关联。本综述讨论了 HDACs 在多种代谢活跃组织中的作用,并强调了它们对组织特异性适应不良和疾病发病机制的贡献。我们还总结了目前的知识空白以及在未来研究中解决这些问题的潜在方法。
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引用次数: 0
A Multiscale Perspective on Chromatin Architecture through Polymer Physics. 通过聚合物物理学透视染色质结构的多尺度视角
IF 5.3 2区 医学 Q1 PHYSIOLOGY Pub Date : 2025-05-01 Epub Date: 2024-11-27 DOI: 10.1152/physiol.00050.2024
Francesca Vercellone, Andrea M Chiariello, Andrea Esposito, Mattia Conte, Alex Abraham, Andrea Fontana, Florinda Di Pierno, Fabrizio Tafuri, Sougata Guha, Sumanta Kundu, Ciro Di Carluccio, Mario Nicodemi, Simona Bianco

The spatial organization of chromatin within the eukaryotic nucleus is critical in regulating key cellular functions, such as gene expression, and its disruption can lead to disease. Advances in experimental techniques, such as Hi-C and microscopy, have significantly enhanced our understanding of chromatin's intricate and dynamic architecture, revealing complex patterns of interaction at multiple scales. Along with experimental methods, physics-based computational models, including polymer phase separation and loop-extrusion mechanisms, have been developed to explain chromatin structure in a principled manner. Here, we illustrate genomewide applications of these models, highlighting their ability to predict chromatin contacts across different scales and to spread light on the underlying molecular determinants. Additionally, we discuss how these models provide a framework for understanding alterations in chromosome folding associated with disease states, such as SARS-CoV-2 infection and pathogenic structural variants, providing valuable insights into the role of chromatin architecture in health and disease.

染色质在真核细胞核内的空间组织对于调控基因表达等关键细胞功能至关重要,其破坏可导致疾病。Hi-C和显微镜等实验技术的进步极大地增强了我们对染色质错综复杂的动态结构的了解,揭示了多种尺度上复杂的相互作用模式。除了实验方法外,我们还开发了基于物理学的计算模型,包括聚合物相分离和环挤出机制,以原则性的方式解释染色质结构。在这里,我们阐述了这些模型在全基因组范围内的应用,强调了它们预测不同尺度染色质接触的能力,以及揭示潜在分子决定因素的能力。此外,我们还讨论了这些模型如何为理解与疾病状态(如 SARS-CoV-2 感染和致病结构变异)相关的染色体折叠变化提供了一个框架,从而为了解染色质结构在健康和疾病中的作用提供了宝贵的见解。
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引用次数: 0
Photoacoustic Imaging of Metabolic Activities across Biological Length Scales. 跨生物长度尺度的代谢活动光声成像。
IF 5.3 2区 医学 Q1 PHYSIOLOGY Pub Date : 2025-05-01 Epub Date: 2024-12-20 DOI: 10.1152/physiol.00010.2024
Gabriella Mankovskii, Eno Hysi

Imaging is ubiquitous with biomedical research and discovery. This article surveys the role of imaging in our understanding of metabolism and introduces photoacoustic imaging as a compelling candidate for providing high-resolution, label-free, and real-time insights into metabolic processes. As a rapidly evolving modality, photoacoustics holds promising preclinical and clinical potential in imaging of metabolism as well as metabolism-related changes.

成像在生物医学研究和发现中无处不在。本文概述了成像在我们对代谢的理解中的作用,并介绍了光声成像作为提供高分辨率,无标签和实时洞察代谢过程的引人注目的候选者。作为一种快速发展的方法,光声学在代谢成像以及代谢相关变化方面具有广阔的临床前和临床潜力。
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引用次数: 0
Physiology in Perspective - May 2025.
IF 5.3 2区 医学 Q1 PHYSIOLOGY Pub Date : 2025-03-18 DOI: 10.1152/physiol.00005.2025
Nikki Forrester
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引用次数: 0
期刊
Physiology
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