LEARNING COMPLEX CUES, REMEMBERING THEIR COMPONENTS: MEMORY FOR COMPLEX STIMULI IN MICE

In natural environments, threats are conveyed by combinations of sensory cues, whereas standard fear conditioning paradigms rely on unimodal stimuli. We developed a Complex Cued Fear Conditioning (CCFC) paradigm in mice to study how multimodal cues are processed in long-term fear memory. Animals were trained with a compound conditioned stimulus consisting of an auditory and a visual cue, paired with a foot shock. Mice trained with the complex stimulus exhibited robust freezing responses to both the compound and individual cues, indicating stable associative memory for each element. Auditory cues evoked stronger responses than visual, with auditory memory maturing rapidly and remaining stable from 1 hour to 7 days, while visual memory showed delayed maturation with freezing gradually increasing over time. Memory for the compound stimulus remained stable even when only one component had fully stabilized, suggesting an asynchronous maturation process. Extinction of one component did not affect the other or the compound stimulus one day after training but extinguished both cues and complex stimulus one week after. Inhibition of protein synthesis disrupted memory for discrete cues but not the compound stimulus one week after training. C-Fos activation during complex stimulus retrieval was observed exclusively in hippocampal CA1 and parietal cortex, indicating differential involvement of brain areas in processing information about the compound stimulus and its separate components. CCFC provides a more ecologically relevant model for studying multimodal associative memory, revealing asynchronous maturation and distinct neural mechanisms underlying complex fear learning. This work was supported by Russian Science Foundation, project 23-78-00010.