Scalable volumetric imaging for ultrahigh-speed brain mapping at synaptic resolution

Area of Science:

• Neuroscience
• Microscopy
• Optical Imaging

Background:

• High-resolution optical imaging speed limits meso-scale brain mapping.
• Understanding brain structures and functional circuits is crucial for neuroscience.

Purpose of the Study:

• Introduce a novel microscopy method, VISoR, for high-throughput, high-quality brain mapping.
• Enable rapid 3D image acquisition of entire brains at synaptic resolution.

Main Methods:

• Volumetric Imaging with Synchronized on-the-fly-scan and Readout (VISoR) utilizes synchronized scanning beam illumination and oblique imaging.
• Continuous imaging of moving samples eliminates motion blur for undistorted 3D image acquisition.
• A comprehensive pipeline for sample preparation, imaging, 3D reconstruction, and quantification was developed.

Main Results:

• The VISoR system acquired a 3D image of an entire mouse brain in 1.5 hours at synaptic spine resolution.
• The method is compatible with immunofluorescence, allowing cell-type specific mapping.
• Analysis of neuronal activation in mice under stress revealed involvement of subcortical areas with significant individual variability.

Conclusions:

• VISoR significantly advances high-throughput, high-quality brain mapping capabilities.
• The technique enables detailed investigation of neuronal activation patterns and their variability.
• Findings highlight the need for large cohorts in studies examining stress response variability.