Innovative Technique Enables Long-Term Brain Activity Monitoring in Freely Moving Mice

Researchers from the University of Tsukuba have introduced a groundbreaking analytical method that enhances the study of neural activity in living animals. This novel technique, named CaliAli (Calcium Imaging inter-session Alignment), allows scientists to track neuronal signals continuously for over 99 days in freely moving mice—a feat that surpasses previous limitations. Such long-term monitoring is crucial for understanding complex brain processes like memory formation and the progression of neurological disorders.

Calcium imaging with ultra-miniature microscopes is a popular method for visualizing brain activity during natural behaviors. However, current analysis techniques face challenges in reliably identifying and tracking individual neurons over extended periods due to shifts in the imaging field and subtle tissue deformations across sessions. These issues hinder longitudinal studies essential for neuroscience.

To address these challenges, the research team developed CaliAli, an advanced analytical framework that systematically aligns data from multiple imaging sessions. The method corrects image misalignments and reconstructs a seamless, continuous video of neural activity. Furthermore, CaliAli includes an optimized algorithm capable of automatically extracting neural signals from aligned images while filtering out noise and redundant detections.

In a significant validation, researchers employed CaliAli to track the same neurons over a period of up to 99 days using standard ultra-miniature microscopes—an unprecedented achievement in this field. This methodology not only improves the accuracy of long-term neural recordings but also opens new avenues for studying brain mechanisms involved in memory, learning, and neurodegenerative diseases.

The findings were published in Nature Communications. This innovative approach promises to advance long-term brain activity studies, providing deeper insights into brain function and disease progression, and could be a valuable tool in neuroscience research.