Mal de Debarquement Syndrome explained by a vestibulo-cerebellar oscillator.

IF 0.8 4区 数学 Q4 BIOLOGY Mathematical Medicine and Biology-A Journal of the Ima Pub Date : 2023-03-13 DOI:10.1093/imammb/dqac016
Bruno Burlando, Viviana Mucci, Cherylea J Browne, Serena Losacco, Iole Indovina, Lucio Marinelli, Franco Blanchini, Giulia Giordano
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引用次数: 1

Abstract

Mal de Debarquement Syndrome (MdDS) is a puzzling central vestibular disorder characterized by a long-lasting perception of oscillatory postural instability that may occur after sea travels or flights. We have postulated that MdDS originates from the post-disembarking persistence of an adaptive internal oscillator consisting of a loop system, involving the right and left vestibular nuclei, and the Purkinje cells of the right and left flocculonodular cerebellar cortex, connected by GABAergic and glutamatergic fibers. We have formulated here a mathematical model of the vestibulo-cerebellar loop system and carried out a computational analysis based on a set of differential equations describing the interactions among the loop elements and containing Hill functions that model input-output firing rates relationships among neurons. The analysis indicates that the system acquires a spontaneous and permanent oscillatory behavior for a decrease of threshold and an increase of sensitivity in neuronal input-output responses. These results suggest a role for synaptic plasticity in MdDS pathophysiology, thus reinforcing our previous hypothesis that MdDS may be the result of excessive synaptic plasticity acting on the vestibulo-cerebellar network during its entraining to an oscillatory environment. Hence, our study points to neuroendocrine pathways that lead to increased synaptic response as possible new therapeutic targets for the clinical treatment of the disorder.

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Debarquement综合征由前庭-小脑振荡器解释。
脱机综合症(MdDS)是一种令人困惑的中枢前庭疾病,其特征是在海上旅行或飞行后可能出现持久的振荡姿势不稳定的感觉。我们假设MdDS起源于一个由循环系统组成的自适应内部振荡器,该系统涉及左右前庭核和左右小脑小叶结节皮质的浦肯野细胞,由gaba能和谷氨酸能纤维连接。我们在此建立了前庭-小脑回路系统的数学模型,并基于一组描述回路元素之间相互作用的微分方程进行了计算分析,该微分方程包含模拟神经元之间输入-输出放电率关系的Hill函数。分析表明,由于阈值的降低和神经元输入输出响应的灵敏度的增加,系统获得了自发的永久振荡行为。这些结果表明突触可塑性在MdDS的病理生理中起作用,从而加强了我们之前的假设,即MdDS可能是前庭-小脑网络在振荡环境中受到过度突触可塑性作用的结果。因此,我们的研究指出,导致突触反应增加的神经内分泌通路可能是临床治疗该疾病的新治疗靶点。
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来源期刊
CiteScore
2.20
自引率
0.00%
发文量
15
审稿时长
>12 weeks
期刊介绍: Formerly the IMA Journal of Mathematics Applied in Medicine and Biology. Mathematical Medicine and Biology publishes original articles with a significant mathematical content addressing topics in medicine and biology. Papers exploiting modern developments in applied mathematics are particularly welcome. The biomedical relevance of mathematical models should be demonstrated clearly and validation by comparison against experiment is strongly encouraged. The journal welcomes contributions relevant to any area of the life sciences including: -biomechanics- biophysics- cell biology- developmental biology- ecology and the environment- epidemiology- immunology- infectious diseases- neuroscience- pharmacology- physiology- population biology
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