Neuronal Encoding of Awareness for Type and Place of Objects in Young and Old Mice  Konstantin Anokhin , Olga Ivashkina; Ksenia Toropova; Anna Gruzdeva; Olga Rogozhnikova; Viktor Plusnin; Ilya Fedotov (Moscow State University, Cente, Lomonosov Moscow State University, Moscow, Russian Federation)   C19

Neuronal encoding of experience-dependent perception has long been in the focus of neuroscience of consciousness. Neurophysiological studies show that when animals become familiar with space or objects, neuronal activity changes due to these aspects of individual experience. However, despite a considerable data, the specific neuronal mechanisms for experience-dependent perception of object and space remains 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. To test this hypothesis, we developed an approach combining optical recording of neuronal activity and assessment of animal behavior during episodes of awareness for the novelty of the type of object (novel object recognition task - NOR) and the novel place of familiar object (object place recognition task - OPR) in young and old mice. We trained young (2-3 months) and old (18-21 months) mice in NOR and OPR tasks and tested them 120 min or 24 h thereafter. We showed that both young and old mice demonstrate awareness for the novelty of type and place of the object, however, none of them maintain this experience for 24 hours. Interestingly, administration of P2 sAPP-mimetic cognitive enhancer led to emergence of long-term memory in old mice. Next, we recorded object-type and object-place awareness-related neural activity in the RSC and the CA1 area of hippocampus of young mice using genetically encoded YtnC calcium sensor and fiber-optic photometry. We found an increase in the number of calcium events in the RSC when animals became aware of a new position of familiar object, and a decrease in the RSC activity when mice became aware of the novelty of object. Using multiphoton microscopy and minimicroscopy we registered GCaMP6 calcium activity of identified RSC and CA1 neurons during NOR and OPR tasks. Different classes of neurons were identified - those demonstrating an increase and decrease of activity during exploration of place and objects, as well as cells that were active during specific behavioral acts. Thus, we showed that both object-type and object-place experience-dependent awareness was expressed in the activity of RSC and CA1 neurons. In the future, we will study this experience-dependent single-cell activity is formed and maintained over time. Supported by RSF 20-15-00283 and RFBR 17-00-00215, 19-315-80020, 17-29-07083, 18-32-20212.