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. In the AON, neurons were broadly tuned to different chemicals, and their responses were strongly modulated by experience. From the AON to hippocampal structures, the selectivity of neurons for specific odorants increased, concurrent with the development of population-level odor representations, which became independent of novelty and familiarity. While both stimulus identity and experience were thus reflected in all regions, their neural representations progressively separated. Our findings provide a potential mechanism for how sensory representations are transformed to support stimulus identification and implicit memories.