Global and local fMRI signals driven by neurons defined optogenetically by type and wiring.
Global and local fMRI signals driven by neurons defined optogenetically by type and wiring.
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尽管基于使用血氧水平依赖（BOLD）信号的功能性MRI的科学和临床脑成像文献快速增长，但是在特定区域中的BOLD信号是否可以由局部兴奋性神经元的激活引起仍然存在争议。这一难题是BOLD解释和应用的核心，对fMRI研究的基础研究和临床应用具有重要意义。使用一种新的集成技术，将输入的光遗传学控制与高场fMRI信号读出统一起来，我们在这里表明，特异性刺激新皮层或丘脑中局部表达CaMKIIα的兴奋性神经元，在刺激位置以经典动力学激发阳性BOLD信号。我们还表明，光遗传学功能磁共振成像（ofMRI）允许可视化的因果关系的影响，不仅由遗传特性和细胞体的位置，而且由轴突投射目标定义的特定细胞类型。最后，我们表明，ofMRI在活的和完整的哺乳动物大脑揭示了BOLD信号在下游目标远离刺激，这表明这种方法可以用来映射控制局部细胞群的全球影响。在这方面，不同于传统的功能磁共振成像研究的基础上的相关性和功能磁共振成像与电刺激，也将直接驱动传入和附近的轴突，这种ofMRI方法提供了因果关系的信息，全球电路招募定义的局部神经元活动模式。这些发现为广泛使用的fMRI BOLD信号提供了经验基础，并且ofMRI的特征定义了一种可能适用于功能电路分析以及功能障碍电路的全球表型分析的有力工具。
Despite a rapidly-growing scientific and clinical brain imaging literature based on functional MRI using blood oxygenation level dependent (BOLD) signals, it remains controversial if BOLD signals in a particular region can be caused by activation of local excitatory neurons. This difficult question is central to the interpretation and utility of BOLD, with major significance for fMRI studies in basic research and clinical applications. Using a novel integrated technology unifying optogenetic control of inputs with high-field fMRI signal readouts, we show here that specific stimulation of local CaMKIIα-expressing excitatory neurons, either in neocortex or thalamus, elicits positive BOLD signals at the stimulus location with classical kinetics. We also show that optogenetic fMRI (ofMRI) allows visualization of the causal effects of specific cell types defined not only by genetic identity and cell body location, but also by axonal projection target. Finally, we show that ofMRI within the living and intact mammalian brain reveals BOLD signals in downstream targets distant from the stimulus, indicating that this approach can be used to map the global effects of controlling a local cell population. In this respect, unlike both conventional fMRI studies based on correlations and fMRI with electrical stimulation which will also directly drive afferent and nearby axons, this ofMRI approach provides causal information about the global circuits recruited by defined local neuronal activity patterns. Together these findings provide an empirical foundation for the widely-employed fMRI BOLD signal, and the features of ofMRI define a potent tool that may be suitable for functional circuit analysis as well as global phenotyping of dysfunctional circuitry.
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影响因子：
14.8
作者：
Zhang F;Gradinaru V;Adamantidis AR;Durand R;Airan RD;de Lecea L;Deisseroth K
通讯作者：
Deisseroth K
影响因子：
25
作者：
Boyden, ES;Zhang, F;Deisseroth, K
通讯作者：
Deisseroth, K
影响因子：
3.3
作者：
Lee, Jin Hyung;Dumoulin, Serge O.;Pauly, John M.
通讯作者：
Pauly, John M.
影响因子：
3.3
作者：
Buxton, RB;Wong, EC;Frank, LR
通讯作者：
Frank, LR
影响因子：
4
作者：
Aravanis, Alexander M.;Wang, Li-Ping;Deisseroth, Karl
通讯作者：
Deisseroth, Karl