ИСТИНА

The ability to form associations is one of the fundamental features of the brain. Pavlov's original work on classical conditioning employed CS that immediately preceded reinforcement. Here, using the model of context preexposure (Rudy, O'Reilly, 2001; Vorobieva et al., 2017), we studied how an engram of a distant past context can become a CS. Mice explored a new context, and then with different delays (from 30 minutes up to 30 days) received an immediate shock in the same environment. We showed that contextual memory engram can be conditioned at all tested intervals. We then used c-Fos expression to map conditioned engram on a whole-brain scale. Associative cortical areas, hippocampal CA1, and amygdala were activated following retrieval of conditioned memory of the context. Next, we analyzed the involvement of hippocampal interneurons and pyramidal neurons in such engram. During memory retrieval in CA1, both excitatory neurons and, to a lesser extent, inhibitory interneurons were activated. Finally, we combined c-Fos imaging with the c-Fos TRAP technique (Guenthner et al., 2013; Ivashkina et al., 2018) to study cellular overlap in initial remembering of context and its conditioning. There was a massive overlap between endogenous c-Fos and Fos-TRAP-trapped neurons in associative cortical areas, hippocampus, and amygdala - neurons that were activated during initial context exploration were reactivated at presentation of the immediate footshock. Our data show that the repetitive activation of the same engram across many brain regions accompanied the formation of associations in the context preexposure task. Supported by Russian Science Foundation 20-15-00283, 23-78-00010.