Optogentic control of epileptic seizures in a network mapped by simultaneous calcium recordings and fMRI

通过同步钙记录和功能磁共振成像绘制的网络中癫痫发作的光控制

• 批准号: 316102862
• 负责人: Professor Dr. Thomas Budde
• 金额: --
• 依托单位: Institut für Physiologie I (Neurophysiologie)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/316102862?language=en
• 关键词: Optogentic; control; epileptic; seizures; network

This project employs a novel and unique combination of optogenetics, fiber-based calcium recordings and functional magnetic resonance imaging (fMRI) to investigate neuronal networks in a rat model of human absence epilepsy, the Genetic Absence Epilepsy Rat from Strasbourg (GAERS) and to explore strategies for optogenetic interventions to interfere with epileptic seizures. Epilepsy affects more than half a million people in Germany, but the exact mechanisms of aberrant network activity in the brain remains elusive. Calcium recordings allow for seizure detection and in depth analysis and interpretation of simultaneously acquired fMRI data. Hemodynamic responses will be derived for specific brain regions and/or seizure phases. Even more, line scanning fMRI allows for read out of cortical layer-specific hemodynamic response functions. Based on accurate hemodynamic response functions, seizure maps with high spatial and temporal specificity will be derived revealing nodes of aberrant network activity and potentially essential, remote seizure choke points. Brain slice experiment at these choke points will systematically investigate and optimize optogenetic approaches, namely silencing of excitatory neurons or activating neurons, to interrupt seizures. Successful strategies will subsequently be transferred and applied in the in vivo model by simultaneous optogenetic-calcium recording-fMRI. Thus, a comprehensive assessment of both neuronal and hemodynamic activity of the epileptic network, including potential choke points at remote brain regions will become possible, and the most promising optogenetic approach to interfere with seizures will be identified.

本项目采用光遗传学、基于纤维的钙记录和功能磁共振成像(FMRI)的新颖而独特的组合来研究人类缺失性癫痫大鼠模型--斯特拉斯堡遗传性缺失性癫痫大鼠(GAERS)的神经元网络，并探索光遗传学干预癫痫发作的策略。在德国，癫痫影响着50多万人，但大脑中异常网络活动的确切机制仍然难以捉摸。钙离子记录可以检测癫痫发作，并对同时获得的功能磁共振数据进行深入分析和解释。血液动力学反应将针对特定的大脑区域和/或癫痫发作阶段而得出。更重要的是，行扫描功能磁共振允许读出皮质层特定的血流动力学反应功能。基于准确的血流动力学反应函数，将得到具有高空间和时间特异性的癫痫地图，以揭示异常网络活动的节点和潜在的必要的、远程的癫痫窒息点。在这些阻塞点的脑片实验将系统地研究和优化光发生方法，即沉默兴奋性神经元或激活神经元，以中断癫痫发作。成功的策略随后将通过同步光遗传-钙记录-功能磁共振在体内模型中转移和应用。因此，全面评估癫痫网络的神经元和血流动力学活动，包括偏远脑区的潜在阻塞点将成为可能，并将确定最有希望的光遗传学方法来干扰癫痫发作。

项目成果

Anesthesia differentially modulates neuronal and vascular contributions to the BOLD signal

• DOI: 10.1016/j.neuroimage.2019.03.057
• 发表时间: 2019-07
• 期刊: NeuroImage
• 影响因子: 5.7
• 作者: Timo Mauritz van Alst;L. Wachsmuth;M. Datunashvili;Franziska Albers;N. Just;T. Budde;C. Faber

Line scanning fMRI reveals earlier onset of optogenetically evoked BOLD response in rat somatosensory cortex as compared to sensory stimulation

• DOI: 10.1016/j.neuroimage.2016.12.059
• 发表时间: 2018-01-01
• 期刊: NEUROIMAGE
• 影响因子: 5.7
• 作者: Albers, Franziska;Schmid, Florian;Faber, Cornelius
• 通讯作者: Faber, Cornelius

A cortical rat hemodynamic response function for improved detection of BOLD activation under common experimental conditions

• DOI: 10.1016/j.neuroimage.2019.116446
• 发表时间: 2020-03-01
• 期刊: NEUROIMAGE
• 影响因子: 5.7
• 作者: Lambers, Henriette;Segeroth, Martin;Faber, Cornelius
• 通讯作者: Faber, Cornelius

Myelination- and immune-mediated MR-based brain network correlates

• DOI: 10.1186/s12974-020-01827-z
• 发表时间: 2020-06-12
• 期刊: JOURNAL OF NEUROINFLAMMATION
• 影响因子: 9.3
• 作者: Cerina, Manuela;Muthuraman, Muthuraman;Meuth, Sven G.
• 通讯作者: Meuth, Sven G.

Functional MRI Readouts From BOLD and Diffusion Measurements Differentially Respond to Optogenetic Activation and Tissue Heating

• DOI: 10.3389/fnins.2019.01104
• 发表时间: 2019-10-24
• 期刊: FRONTIERS IN NEUROSCIENCE
• 影响因子: 4.3
• 作者: Albers, Franziska;Wachsmuth, Lydia;Faber, Cornelius
• 通讯作者: Faber, Cornelius