Neuronal threshold functions: Determining symptom onset in neurological disorders

IF 6.7 2区 医学 Q1 NEUROSCIENCES Progress in Neurobiology Pub Date : 2024-10-09 DOI:10.1016/j.pneurobio.2024.102673
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Abstract

Synaptic networks determine brain function. Highly complex interconnected brain synaptic networks provide output even under fluctuating or pathological conditions. Relevant to the treatment of brain disorders, understanding the limitations of such functional networks becomes paramount. Here we use the example of Parkinson’s Disease (PD) as a system disorder, with PD symptomatology emerging only when the functional reserves of neurons, and their interconnected networks, are unable to facilitate effective compensatory mechanisms. We have denoted this the “threshold theory” to account for how PD symptoms develop in sequence. In this perspective, threshold functions are delineated in a quantitative, synaptic, and cellular network context. This provides a framework to discuss the development of specific symptoms. PD includes dysfunction and degeneration in many organ systems and both peripheral and central nervous system involvement. The threshold theory accounts for and explains the reasons why parallel gradually emerging pathologies in brain and peripheral systems generate specific symptoms only when functional thresholds are crossed, like tipping points. New and mounting evidence demonstrate that PD and related neurodegenerative diseases are multisystem disorders, which transcends the traditional brain-centric paradigm. We believe that representation of threshold functions will be helpful to develop new medicines and interventions that are specific for both pre- and post-symptomatic periods of neurodegenerative disorders.
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神经元阈值功能:确定神经系统疾病的症状发作。
突触网络决定大脑功能。即使在波动或病理条件下,高度复杂的互联大脑突触网络也能提供输出。在治疗脑部疾病时,了解这种功能网络的局限性至关重要。在此,我们以帕金森病(PD)为例,将其作为一种系统紊乱,只有当神经元及其互连网络的功能储备无法促进有效的补偿机制时,帕金森病的症状才会出现。我们将此称为 "阈值理论",以解释帕金森病症状是如何依次出现的。从这一角度来看,阈值功能是在定量、突触和细胞网络的背景下进行描述的。这为讨论特定症状的发展提供了一个框架。帕金森病包括许多器官系统的功能障碍和退化,并涉及周围和中枢神经系统。阈值理论说明并解释了为什么大脑和外周系统中平行逐渐出现的病理现象只有在跨越功能阈值(如临界点)时才会产生特定症状。越来越多的新证据表明,帕金森病和相关的神经退行性疾病是多系统疾病,这超越了传统的以大脑为中心的范式。我们相信,阈值功能的表征将有助于开发针对神经退行性疾病症状前期和后期的新药和干预措施。
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来源期刊
Progress in Neurobiology
Progress in Neurobiology 医学-神经科学
CiteScore
12.80
自引率
1.50%
发文量
107
审稿时长
33 days
期刊介绍: Progress in Neurobiology is an international journal that publishes groundbreaking original research, comprehensive review articles and opinion pieces written by leading researchers. The journal welcomes contributions from the broad field of neuroscience that apply neurophysiological, biochemical, pharmacological, molecular biological, anatomical, computational and behavioral analyses to problems of molecular, cellular, developmental, systems, and clinical neuroscience.
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