Abstract
In recent years, the combination of whole-brain immunolabelling, light sheet fluorescence microscopy (LSFM), and subsequent registration of data with a common reference atlas has enabled 3D visualization and quantification of fluorescent markers or tracers in the adult mouse brain. Today, the Common Coordinate Framework version 3 (CCFv3), developed by the Allen Institute of Brain Science (AIBS), is widely used as the standard brain atlas for registering LSFM data.
However, AIBS CCFv3, which is based on histological processing and imaging modalities different from those used for LSFM imaging, results in discrepancies in tissue contrast and morphology. To address these differences and enhance accuracy and speed in registering and quantifying LSFM-imaged whole-brain data, we created an optimized digital mouse brain atlas based on immunolabelled and solvent-cleared brains.
Key findings:
- Compared to the AIBS CCFv3 atlas, our atlas enabled faster and more accurate mapping of neuronal activity measured by c-Fos expression, particularly in the hindbrain.
- The utility of the LSFM atlas was demonstrated through a comparison of whole-brain quantitative changes in c-Fos expression following acute semaglutide administration in both lean and diet-induced obese (DIO) mice.
By integrating the optimized atlas with an improved algorithm for c-Fos detection, the LSFM atlas facilitates unbiased and computationally efficient characterization of drug effects on whole-brain neuronal activity patterns.
In conclusion, we established an optimized reference atlas for more precise mapping of fluorescent markers, including c-Fos, in mouse brains processed for LSFM, providing a valuable tool for future neuroscience research.
