Zhao and coauthors have developed a new miniature head-mounted two-photon microscope with enhanced capabilities for large field-of-view brain imaging in freely moving mice. The design can perform sub-cellular resolution imaging over 1000 x 788 μm² fields at a 9 Hz frame rate, fast enough to measure neural activity with use of genetically encoded Ca²⁺ indicators. The capability to perform two-photon imaging with infrared light as opposed to one-photon with UV-visible wavelengths allows greater penetration depth in scattering brain tissue. An additional feature of this miniature microscope is the axial scanning capability with adjustment through a 500-micron depth. The ability to image over this large volume allows measurements of activity in multiple brain regions providing studies of connectivity in neural circuits. With a miniaturized system, the brain can be studied under naturalistic behaviors such as navigation to avoid predators or locate food, social behavior and mating. These types of studies can lead to new understanding that can assist with clinical care for those suffering from neurological disorders including autism and Alzheimer’s disease.

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