Synthetic imager to record cortical neural activity over whole cranium in freely-behaving animals

合成成像仪记录自由行为动物整个颅骨的皮质神经活动 了解动物行为过程中不同大脑区域的信息流是研究动物行为的关键一步。 破译大脑是如何工作的它需要记录大量神经元群体的神经活动 同时保持高的时空分辨率。虽然功能磁共振成像可以提供整个大脑 活动图，它缺乏空间和时间分辨率。传统的光学方法受到 视场和空间分辨率之间的折衷。此外，大多数成像系统是 体积庞大，受试动物必须处于头部固定的状态，这限制了 可以研究。 在这个建议中，我们介绍了一种新的成像模式，克服了上述限制。我们提出了一个 集成成像仪，可以记录自由行为小鼠整个皮层表面的神经活动。它 利用先进的微加工技术、现代计算光学和统计 去卷积和去混合方法。成像系统是一个薄而灵活的堆栈，包括 微透镜阵列层、可编程InGaN LED阵列层和光电探测器阵列层。可以 共形植入小鼠大脑皮层表面-就好像它是一个新的头骨，并记录神经元的 当动物自由活动时，大脑皮层的活动。可编程LED的独特功能 阵列有助于准确提取神经元位置和荧光背景。使用 通过使用计算光学和现代分离算法，可以提取潜在的神经活动。 与传统的光学显微镜相比，该成像系统扩展了视场 两个数量级，同时保持良好的时空分辨率。这个植入式成像器 将彻底改变功能成像领域，适用于许多研究大脑皮层的实验室。 动物行为中的神经活动。此外，所提出的装置可扩展以包括 光刺激来操纵整个皮层表面的神经活动;它也可以作为原型 可穿戴设备来监测人类的大脑活动。该设备将实现一个关键的飞跃 实现BRAIN计划的目标。

Synthetic imager to record cortical neural activity over whole cranium in freely-behaving animals Understanding information flow across different brain regions during animal behavior is a key step to decipher how the brain works. It requires recording neural activities over a large neuronal population simultaneously, while maintaining a high spatiotemporal resolution. While fMRI can provide whole brain activity maps, it lacks both spatial and temporal resolutions. Conventional optical methods suffer from a tradeoff between the field of view and spatial resolution. Furthermore, majority of the imaging systems are bulky and the tested animals have to be set up in the head-fixed condition, which limits the behaviors that can be studied. In this proposal, we introduce a novel imaging modality which overcomes the above limits. We propose an integrated imager that can record neural activity on the whole cortical surface in freely-behaving mice. It leverages advanced microfabrication technologies, modern computational optics, and statistical deconvolution and demixing methods. The imaging system is a thin and flexible stack that consists of a microlens array layer, a programmable InGaN LED array layer and a photodetector array layer. It can be implanted conformally on the cortical surface of mice brain – as if it is a new skull, and record the neural activities over the cortex while the animal is freely behaving. The unique feature of the programmable LED array facilitates an accurate extraction of neuron locations and fluorescence background. Using computational optics and the modern demixing algorithm, the underlying neural activity can be extracted. Compared to the conventional optical microscopes, the proposed imaging system expands the field of view by two-orders of magnitude, while maintaining a good spatiotemporal resolution. This implantable imager will revolutionize the field of functional imaging and is applicable to many labs who are investigating cortical neural activity during animal behaviors. Furthermore, the proposed device is extendable to include photostimulation to manipulate neural activity over the whole cortical surface; it also serves as a prototype of wearable device to monitor brain activity of humans. The proposed device will enable a critical leap towards achieving the goals of the BRAIN initiative.