NeuropixelsUltra: Dense arrays for stable, unbiased, and cell type-specific electrical imaging

总结/摘要 理解认知和行为的神经机制需要 测量神经元群体的动力学和相互作用的能力 许多脑区。电生理学技术提供了测量这一点的能力 以思维的速度在表层和深层结构中活动。的最新进展 电生理学已经大大增加了数据的数量、质量和采集的容易性， 从而有意义地减少了理解全球大脑回路的障碍， 行为一个重要的剩余挑战是优化器件特性， 进一步拓宽利用面，提高数据质量，加快研究步伐。在 特别地，现有技术的位点密度在空间上太粗糙而不能检测某些细胞类型， 神经元过程;在大脑中稳定记录神经元仍然具有挑战性 运动;数据预处理仍然是实验速度的主要限制因素。 本提案将通过生产和评估一种新器械来解决这些局限性， > 10倍于现有技术的记录位点数量，对应于 密度更高。因此，该装置的功能类似于高分辨率电子照相机 在大脑中，能够成像微小的电场，并能够利用技术 从光学如图像配准的记录稳定性。 我们将通过量化新探头的增加来验证和开发新探头的特性 检测大量神经元类型的能力;通过测试和发展他们的跟踪能力 神经元在大脑运动中使用受控条件;通过改进算法， 数据预处理的自动化;以及进行多模态地面实况实验。 这些探头将超越解决技术限制，还提供新类型的 数据：“电形态学”形状的电成像将能够增强细胞类型 体内神经元生物物理模型的鉴定和验证。 我们将分发新的探头，沿着用户友好的软件，以利用 他们改进的特性，"测试“实验室特别感兴趣的研究关键 科学机遇的领域。这些领域包括树突计算，自由移动 行为和小脑功能，这种直接传播将迅速加速他们的行为， 影响科学进步。

Summary/Abstract Understanding the neural mechanisms underpinning cognition and behavior requires the ability to measure the dynamics and interactions of populations of neurons spread across many brain regions. Electrophysiological techniques provide the ability to measure this activity across superficial and deep structures at the speed of thought. Recent advances in electrophysiology have massively increased data quantity, quality, and ease of acquisition, thereby meaningfully reducing barriers to understanding the global brain circuits underlying behavior. A significant remaining challenge is to optimize device characteristics in order to further broaden utility, improve data quality, and accelerate the pace of research. In particular, state of the art site density is spatially too coarse to detect some cell types and neuronal processes; it remains challenging to record neurons stably in the face of brain motion; and data preprocessing is still a major limiting factor in the pace of experiments. This proposal will address these limitations by producing and evaluating a new device with >10x the number of recording sites than state-of-the-art, corresponding to an order of magnitude higher density. This device thus functions like a high-resolution electrical camera in the brain, able to image tiny electrical fields and capable of capitalizing on techniques from optics such as image registration for recording stability. We will validate and develop the new probe's characteristics by quantifying their increased ability to detect a large range of neuron types; by testing and developing their ability to track neurons across brain motion using controlled conditions; by improving algorithms towards automation of data preprocessing; and by conducting multi-modal ground-truth experiments. These probes will go beyond solving technical limitations, additionally providing new types of data: electrical imaging of `electro-morphological' shapes will enable enhanced cell-type identification and validation of neuronal biophysical models in vivo. We will disseminate the new probes, along with user-friendly software to take advantage of their improved characteristics, to `beta-tester' labs specifically interested in studying key areas of scientific opportunity. These areas include dendritic computation, freely-moving behavior, and cerebellar function, and this direct dissemination will rapidly accelerate their impact on scientific advancement.