MiniXL: An open-source, large field-of-view epifluorescence miniscope enabling single-cell resolution and multi-region imaging in mice

Capturing the intricate dynamics of neural activity in freely behaving animals is essential for understanding the neural mechanisms underpinning specific behaviors. Miniaturized microscopy enables investigators to track population activity at the cellular level, but the field of view (FOV) of these microscopes has often been limited and do not support multi-brain region imaging. To fill this technological gap, we have developed the eXtra Large FOV Miniscope (MiniXL) for mice, a 3.5-gram miniaturized microscope with an FOV measuring 3.5 mm in diameter. We demonstrate the capabilities of the MiniXL through large-scale neuronal population records in hippocampal dorsal CA1. We also demonstrate simultaneous multi-brain region imaging across bilateral medial prefrontal cortex (mPFC) and mPFC and nucleus accumbens (NAc) during complex social behavior and stably track cells across multiple days. As with all microscopes in the UCLA Miniscope ecosystem, the MiniXL is fully open-source and designed to be shared with the neuroscience community to lower the barriers for adoption of this technology.