Wide field of view 3D microscopy for calcium imaging and photostimulation

项目摘要/摘要 精神疾病，包括精神分裂症、抑郁症和自闭症谱系障碍，仍然很差 可以理解，尽管很明显，它们主要代表皮质障碍。大脑皮质是大脑的主要部位 更高的精神功能，尽管进行了广泛的研究，但关于皮质如何工作仍然没有统一的理论。 这在一定程度上是因为神经科学家传统上依赖微电极来记录 单个细胞的活动。然而，大脑皮质回路是由数百万个神经元组成的，这是可以想象的 单靠单个细胞的测量不足以解开大脑的功能。光学成像 处理这种突现水平的神经元回路活动的技术，使之能够成像神经元的活动 在体外和体内进行组合，同时保持单细胞分辨率，这是大脑成像技术 例如核磁共振或正电子发射计算机断层扫描，是做不到的。此外，基因编码的光敏蛋白的开发 (光遗传学)和光化学(笼式)化合物不仅提供了成像活性的机会 很多神经元，但也要对它们进行光学控制。 光遗传学的进步导致了双光子显微镜与空间光学相结合的发展 光调制器(SLM)，允许客户将激光束分割成全息图案，该图案可以 用于同时对3D中的神经元活动或光激活进行成像。多个商业可用 现在提供显微镜。此外，研究人员正在定制自己的显微镜，以降低成本 购买新的商用显微镜的替代方案。Meadowlark Optics(MLO)SLM是 由于前所未有的响应时间比竞争对手的SLM快8倍而被优先利用， 使得对大脑功能进行更复杂的研究成为可能。然而，SLM的有限分辨率导致了研究 在较小体积和低填充因子的情况下，会导致光学损耗。为了解决这些担忧，MLO提出了 开发了一种高速(142赫兹到500赫兹)、高填充系数(95%)、高分辨率的SLM。减少 成本和上市时间MLO建议利用现有的底板，总共节省100万美元， 和一年的发展。Meadowlark将在第一阶段内实现一个原型系统，并将利用 内部资金完成产品。

Project Summary/Abstract Mental disease, including schizophrenia, depression and autism spectrum disorders, are still poorly understood, although it is clear that they mostly represent cortical disorders. The cortex is the primary site of higher mental functions, and despite extensive research, there is still no unified theory of how the cortex works. This is partly due to the fact that neuroscientists have traditionally relied on microelectrodes to record the activity of individual cells. However, cortical circuits are composed of millions of neurons and it is conceivable that single cell measurements alone will not be sufficient to unravel function of the brain. Optical imaging techniques tackle this emergent level of neuronal circuit activity and enable to image the activity of neuronal ensembles, in vitro and in vivo, while preserving single cell resolution, something that brain imaging techniques such as MRI or PET, cannot do. Moreover, the development of genetically encoded photosensitive proteins (optogenetics) and optochemical (caged) compounds offers the opportunity to not only image the activity of many neurons but also to optically control them. Advances in optogenetics has led to the development of two-photon microscopes combined with spatial light modulators (SLM), that allow the customer to split the laser beam into a holographic pattern that can be used to image activity or photoactivate neurons simultaneously in 3D. Multiple commercially available microscopes are now offered. Additionally researchers are customizing their own microscopes as a low cost alternative to purchasing new commercially available microscopes. The Meadowlark Optics (MLO) SLM is preferentially utilized due to the unprecedented response time a factor of 8 faster than competing SLMs, enabling more complex studies of brain function. However, the limited resolution of the SLM leads to studies over a smaller volume, and low fill factor leads to optical losses. To address these concerns MLO is proposing the development of a high speed (142 Hz to 500 Hz), high fill factor (95%), high resolution SLM. To reduce cost, and time to market MLO proposes to utilize an existing backplane, representing a total savings of $1M, and 1 year of development. Meadowlark will realize a prototype system within the Phase I, and will utilize internal funds to complete the product.