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

基本信息

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

项目摘要

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.

该项目采用光遗传学、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失神癫痫大鼠模型（来自斯特拉斯堡的遗传性失神癫痫大鼠 (GAERS)）中的神经元网络，并探索光遗传学干预策略以干扰癫痫发作。德国有超过 50 万人患有癫痫症，但大脑异常网络活动的确切机制仍然难以捉摸。钙记录可用于癫痫发作检测以及对同时采集的功能磁共振成像数据进行深入分析和解释。将针对特定的大脑区域和/或癫痫发作阶段得出血流动力学反应。更重要的是，线扫描功能磁共振成像可以读取皮质层特定的血流动力学反应函数。基于准确的血流动力学反应函数，将得出具有高空间和时间特异性的癫痫发作图，揭示异常网络活动的节点和潜在重要的远程癫痫发作阻塞点。在这些阻塞点进行脑切片实验将系统地研究和优化光遗传学方法，即抑制兴奋性神经元或激活神经元，以中断癫痫发作。随后，成功的策略将通过同步光遗传学-钙记录-功能磁共振成像转移并应用到体内模型中。因此，对癫痫网络的神经元和血流动力学活动（包括远程大脑区域的潜在阻塞点）进行全面评估将成为可能，并且将确定干扰癫痫发作的最有希望的光遗传学方法。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Multimodal Functional Neuroimaging by Simultaneous BOLD fMRI and Fiber-Optic Calcium Recordings and Optogenetic Control

DOI：
10.1007/s11307-017-1130-6
发表时间：
2018-04-01
期刊：
MOLECULAR IMAGING AND BIOLOGY
影响因子：
3.1
作者：
Albers, Franziska;Wachsmuth, Lydia;Faber, Cornelius
通讯作者：
Faber, Cornelius

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
通讯作者：
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