Miniscope-LFOV: A large field of view, single cell resolution, miniature microscope for wired and wire-free imaging of neural dynamics in freely behaving animals

We present a large field of view (FOV) open-source miniature microscope (MiniLFOV) designed to extend the capabilities of the UCLA Miniscope platform to large-scale, single cell resolution neural imaging in freely behaving large rodents and head-fixed mice. This system is capable of multiple imaging configurations, including deep brain imaging using implanted optical probes and cortical imaging through cranial windows. The MiniLFOV interfaces with existing open-source UCLA Miniscope DAQ hardware and software, can achieve single cell resolution imaging across a 3.6 × 2.7 mm field of view at 23 frames per second, has an electrically adjustable working distance of up to 3.5 mm±150 µm using an onboard electrowetting lens, incorporates an absolute head-orientation sensor, and weighs under 14 grams. The MiniLFOV provides a 30-fold larger FOV and yields 20-fold better sensitivity than Miniscope V3, and a 12-fold larger FOV with 2-fold better sensitivity than Miniscope V4. Power and data transmission are handled through a single, flexible coaxial cable down to 0.3 mm in diameter facilitating naturalistic behavior. We validated the MiniLFOV in freely behaving rats by simultaneously imaging >1000 GCaMP7s expressing neurons in the CA1 layer of the hippocampus and in head-fixed mice by simultaneously imaging ~2000 neurons in the mouse dorsal cortex through a 4 × 4 mm cranial window. For freely behaving experiments, the MiniLFOV supports optional wire-free operation using a 3.5 g wire-free data acquisition expansion board which enables close to 1-hour of wire-free recording with a 400 mAh (7.5 g) on-board single-cell lithium-polymer battery and expands wire-free imaging techniques to larger animal models. We expect this new open-source implementation of the UCLA Miniscope platform will enable researchers to address novel hypotheses concerning brain function in freely behaving animals.