Development of a Whole-brain Imaging System at Subcellular Resolution for Analysis of Animal Models of Neuropsychiatric Disorders

Abstract

Brain functions are performed by highly interconnected neurons distributed across the whole brain. Imaging of the whole brain at subcellular resolution is crucial for precise understanding of the pathological and therapeutic mechanisms of neuropsychiatric disorders; however, microscopic imaging of the whole brain remains a challenge due to the trade-offs between imaging speed and spatial resolution. To overcome this, we have recently developed block-face serial microscopy tomography (FAST), which is a novel serial-section imaging system using high-speed spinning-disk confocal microscopy. FAST enables high-throughput imaging of whole mouse brains (2.4 h per brain at maximum speed) and can be applied to nonhuman primate whole brains and human postmortem brains. Whole-brain neuronal activation mapping using FAST and Arc-dVenus mice reveals differences in brain-wide activation patterns between acute and chronic stress exposure. These applications of FAST are expected to contribute to unbiased and hypothesis-free analyses for understanding the anatomical and functional relationships of the brain underlying disease and pharmacotherapy.