Experience shapes the transformation of olfactory representations along the cortico-hippocampal pathway

Perception relies on the neural representation of sensory stimuli. Primary sensory cortical representations have been extensively studied, but how sensory information propagates to memory-related multisensory areas has not been well described. We studied this question in the olfactory cortico-hippocampal pathway in mice. We recorded single units in the anterior olfactory nucleus (AON), the anterior piriform cortex (aPCx), lateral entorhinal cortex (LEC), the hippocampal CA1 subfield, and the subiculum (SUB) while animals performed a non-associative learning paradigm involving novel and familiar stimuli. Novel stimuli evoked larger responses than familiar stimuli in the AON, whereas in hippocampal areas, novelty was reflected by the number of responsive neurons. In parallel, odorant selectivity increased along the pathway. While both stimulus identity and experience were thus reflected in all regions, their neural representations gradually separated. Our findings provide a potential mechanism for how sensory representations are transformed to support stimulus identification and implicit memories.