ИСТИНА

Neuronal encoding of environmental information has long been in the focus of neuroscience. However, despite a considerable amount of experimental data, the specific neural bases of space and objects encoding remain an open question. In this work, we test the hypothesis that neurons in different regions of the brain, hippocampus and retrosplenial cortex (RSC) encode spatial and object information respectively and that natural aging impairs these two forms of memory differently. For this purpose, we developed an approach combining optical recording of neuronal activity and assessment of animal behavior during novel object recognition (NOR) and object place recognition (OPR) tasks. First, we recorded the object-type and object-place related calcium activity in the RSC and hippocampus CA1 of mice using genetically encoded calcium sensor and fiber-optic photometry. We found an increase in number of calcium events in the RSC when animals examined new position of the familiar object. We also discovered a decrease in the RSC activity during exploration of a novel object. Next, we developed the object-in-place recognition task in 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. We showed that mice actively explored MHC with cues and objects and successfully formed both place and object recognition memories. Using multiphoton microscopy and NVista minimicroscopy we registered calcium activity of identified RSC and CA1 neurons during NOR and OPR tasks performed in the MHC. CA1 neurons demonstrate a subsequent increase in activity in novel situations like adding a new object or moving it to a new place. We also found CA1 location-specialized cells, and these specializations did not depend on the position and type of objects in the MHC. Thus, we have shown that hippocampus encodes information about space, including objects in it, but regardless of their type and position. We also performed a population analysis of the activity of neurons in the RSC, and showed, that this area is activated specifically with the type of objects, regardless of their position. We also examined what forms of object memory are affected in old mice, and whether it is possible to restore the age-impaired memory pharmacologically. We trained young (2-3 months) and old (18-21 months) mice in NOR and OPR tasks and then tested short-term (120 min after the training) and long-term memory (24 hours after the training). We showed that both young and old mice demonstrate short-term NOR and OPR memories, and that s-APP mimetic P2 cognitive enhancer did not potentiate this memory. On the other hand, both old and young mice failed to form NOR and OPR long-term memories. Interestingly, administration of P2 produced long-term memory restoration only in old mice. These results support the hypothesis about the independent encoding of information about space in the hippocampus and information about objects in the retrosplenial cortex. However, the mechanisms of dynamic interactions betweenthe hippocampus and the retrosplenial cortex for encoding complete information about an object in space have yet to be revealed. We will also analyze the neuronal activity changes during NOR and OPR tasks in old animals.