ИСТИНА

Though cellular mechanisms of associative memory are commonly studied to a single discrete stimulus, natural learning often involves complex stimuli composed of several sensory modalities. There are two alternative theories of the neural mechanism of such learning. Elemental learning theory suggests that each component of compound signal is encoded and associated separately. Configural theory predicts that representation of the entire compound signal is formed and associated with second event. We used mouse Pavlovian fear conditioning to a compound cue (CC) consisted of auditory and visual stimuli. We showed that memory about the CC and its separate components matures differently: memory for the CC and the tone component was expressed as freezing behavior starting from 24 h after training, whereas the light component produced significant freezing only starting from the third day. Similar dissociation of these memories was observed in extinction experiments. Extinction of one of the components of the CC memory 24 h after training did not affect memory about another component or the whole CC. However, 7 d after training extinction of one component of the CC memory resulted in full memory extinction. To identify neuronal substrates of the CC engram we performed c-Fos mapping of neuronal activity in the mouse brain. We found that CC learning resulted in significant activation of prelimbic cortex and amygdala. Retrieval of CC memory and its separate components 7 d after training produced significant activation of prelimbiс and parietal association cortices, whereas amygdala was activated only after the whole CC retrieval. We also found that pattern of CC retrieval-induced c-Fos expression changed between 1 and 7 d after learning. Finally, we performed in vivo two-photon imaging of learning-induced and retrieval-induced c-Fos neuronal activity in the parietal associative cortex of c-Fos-EGFP transgenic mice. We showed that the number of highly-active neurons increased in the trained compared to the control mice. We analyzed neurons with high с-Fos-EGFP expression only in one of the retrieval sessions and found three types of neuronal responses: light-, sound- and CC-induced. Our data suggest that engram of the complex conditioned signal includes both configural and elemental neuronal representations. These representations have different neuronal substrates, show different dynamics of consolidation and can be used separately in the animal behavior. Supported by RSCF 14-15-00685