All-optical imaging and patterned stimulation with a one-photon endoscope

Abstract

While in vivo calcium imaging makes it possible to record activity in defined neuronal populations with cellular resolution, optogenetics allows selective manipulation of neural activity. Recently, these two tools have been combined to stimulate and record neural activity at the same time, but current approaches often rely on two-photon microscopes that are difficult to use in freely moving animals, or one-photon fiberscopes with benchtop-based digital micromirror devices that limit system portability. To address these limitations, we have developed a new integrated system combining a one-photon endoscope and a digital micromirror device for simultaneous calcium imaging and precise optogenetic photo-stimulation (Miniscope with All-optical Patterned Stimulation and Imaging, MAPSI). Using this system, we were able to successfully image striatal neurons from either the direct pathway or the indirect pathway while simultaneously activating any neuron of choice within the field of view or synthesizing arbitrary spatio-temporal patterns of photo-stimulation in freely moving mice. We could also select neurons based on their relationship with behavior and recreate the behavior by mimicking the natural neural activity with photo-stimulation. MAPSI thus provides a powerful tool for in vivo interrogation of neural circuit function.