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The goal of our study was to investigate neuronal specializations in the retrosplenial cortex to a new environment and objects in it. To this end, we used in vivo two-photon calcium imaging in mice during object-in-place recognition task. As two-photon imaging requires head fixation of animals, we used the Mobile Home Cage (MHC, Neurotar Ltd) setup – an air-lifted mobile cage, where a head-fixed animal can move around and explore the environment. First, we developed the object-in-place recognition task in the MHC on C57 Bl/6 mice with implanted headposts (Neurotar Ltd). Mice were habituated to the MHC conditions during 14 days with session time increasing from 10 to 50 min. The object-in-place task consisted of 7 sessions. During sessions mice explored empty MHC, MHC with new proximal cues, MHC with two novel objects, MHC with one of the familiar objects displaced (place recognition task), and MHC with a familiar and a novel object (object recognition task). We showed that mice actively explored MHC with cues and objects. In the place recognition task, mice spent more time exploring and sniffing the familiar object in the new location, demonstrating place recognition memory. In the object recognition task, animals preferentially explored and sniffed the novel object, demonstrating object recognition memory. After we successfully developed the MHC-based object-in-place task, we performed two-photon calcium imaging using GCaMP6 in the retrosplenial cortex during task sessions. We showed the responses of the retrosplenial neurons to different objects and locations through the imaging sessions. Supported by RSCF 14-15-00685 and RFBR 17-04-02054