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Effects of transcranial magnetic stimulation on limbic network properties in rat models of psychiatric phenotype

经颅磁刺激对精神表型大鼠模型边缘网络特性的影响

基本信息

批准号：
374523639
负责人：
Professor Dr. Klaus Funke
金额：
--
依托单位：
Abteilung für Neurophysiologie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2017
资助国家：
德国
起止时间：
2016-12-31 至 2021-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/374523639?language=en
关键词：
Effects transcranial magnetic stimulation limbic

项目摘要

The findings of human studies indicate that repetitive transcranial magnetic stimulation (rTMS) bears the potential to correct pathological neuronal activity associated with a spectrum of psychiatric diseases. Depending on the stimulus pattern (frequency, temporal structure) applied, cortical excitability can be raised or decreased. Little is know about the cellular effects of rTMS but numerous human and animal studies indicate an involvement of synaptic plasticity. However, since acute stimulation effects rarely last longer than 60 minutes, a direct induction of long-term potentiation or depression (LTP, LTD) is less likely than the induction of metaplasticity via homeostatic processes. Currently, a modulation of the cortical balance of excitation and inhibition via changes of the activity of GABAergic interneurons is discussed, in particular a regulation of LTP/LTD induction by disinhibition as is also discussed for natural processes of learning and activity driven development. Our own studies showed rTMS-induced modulation of the activity of cortical inhibitory interneurons, in particular those expressing the calcium binding protein parvalbumin (PV+) and belonging to the group of fast-spiking interneurons. Just the latter appear to play a key role in the development and persistence of neuropsychiatric diseases. Using electrophysiological, optical, pharmacological and immunhistochemical methods we like to study how neuronal excitability and plasticity and network activity may be altered in rat models of psychiatric phenotypes and how rTMS is able to change these processes in comparison to normal control rats. In addition, response properties of pre-labeled PV+ interneurons will be studied. In parallel we will further develop a system allowing the acute suprathreshold magnetic stimulation of brain slices while recording network activity induced by different orientations of the induced electric field. In the course of the planed studies we expect important findings regarding the kind of network activity induced by rTMS in vivo, whether they differ between pathological and healthy tissue and how the changes induced by rTMS may be beneficial to correct neuronal activity in a way to treat or prevent the progress of neuropsychiatric diseases.

人体研究结果表明，重复经颅磁刺激（rTMS）具有纠正与一系列精神疾病相关的病理性神经元活动的潜力。根据所施加的刺激模式（频率、时间结构），皮质兴奋性可以升高或降低。人们对 rTMS 的细胞效应知之甚少，但大量人类和动物研究表明它与突触可塑性有关。然而，由于急性刺激效应很少持续超过 60 分钟，因此直接诱导长时程增强或抑制 (LTP, LTD) 的可能性小于通过稳态过程诱导化塑性。目前，讨论了通过改变 GABA 能中间神经元的活性来调节皮质的兴奋和抑制平衡，特别是通过去抑制来调节 LTP/LTD 诱导，这也讨论了学习和活动驱动发展的自然过程。我们自己的研究表明，rTMS 诱导调节皮质抑制性中间神经元的活性，特别是那些表达钙结合蛋白小白蛋白 (PV+) 并属于快速尖峰中间神经元组的神经元。后者似乎在神经精神疾病的发生和持续过程中发挥着关键作用。我们喜欢使用电生理学、光学、药理学和免疫组织化学方法来研究精神表型大鼠模型中神经元兴奋性、可塑性和网络活动如何改变，以及与正常对照大鼠相比，rTMS 如何能够改变这些过程。此外，还将研究预标记的 PV+ 中间神经元的响应特性。与此同时，我们将进一步开发一种系统，允许对脑切片进行急性超阈值磁刺激，同时记录由不同方向的感应电场引起的网络活动。在计划的研究过程中，我们期待关于 rTMS 在体内诱导的网络活动类型、病理组织和健康组织之间是否存在差异以及 rTMS 诱导的变化如何有利于纠正神经元活动以治疗或预防神经精神疾病进展的重要发现。