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

项目总结/摘要 精神疾病，包括精神分裂症，抑郁症和自闭症谱系障碍， 虽然很明显，它们主要代表皮质疾病。大脑皮层是 更高的心理功能，尽管进行了广泛的研究，但仍然没有关于皮质如何工作的统一理论。 这部分是由于神经科学家传统上依赖于微电极来记录神经元的活动。 单个细胞的活动。然而，皮层回路由数百万个神经元组成， 单细胞测量不足以揭示大脑的功能。光学成像 技术解决了神经元回路活动的这种紧急水平， 集合，在体外和体内，同时保持单细胞分辨率，大脑成像技术 如核磁共振成像或正电子发射断层扫描等。此外，基因编码的光敏蛋白的发展 （光遗传学）和光化学（笼状）化合物提供了机会，不仅形象的活动， 许多神经元，但也光学控制它们。 光遗传学的进步导致了双光子显微镜与空间成像相结合的发展。 光调制器（SLM），允许客户将激光束分成全息图案， 用于在3D中同时成像活动或光激活神经元。多种市售产品 现在有显微镜了。此外，研究人员正在定制他们自己的显微镜，作为一种低成本 替代购买新的商用显微镜。Meadowlark Optics（MLO）SLM 由于前所未有的响应时间比竞争SLM快8倍， 从而使大脑功能的研究更加复杂。然而，由于可持续土地管理的分辨率有限， 而低填充因子导致光损耗。为了解决这些问题，MLO建议 高速（142 Hz至500 Hz）、高填充因子（95%）、高分辨率SLM的开发。减少 成本和上市时间MLO建议利用现有背板，总共节省100万美元， 一年的发展。Meadowlark将在第一阶段实现原型系统，并将利用 内部资金来完成产品。

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.