Negative valence encoding in the lateral entorhinal cortex during aversive olfactory learning

Olfactory learning is widely regarded as a substrate for animal survival. The exact brain areas involved in olfactory learning and how they function at various stages during learning remain elusive. Here, we investigate the role of the lateral entorhinal cortex (LEC) and the posterior piriform cortex (PPC), two important olfactory areas, in aversive olfactory learning. We find that the LEC is involved in the acquisition of negative odor value during olfactory fear conditioning, whereas the PPC is involved in the memory-retrieval phase. Furthermore, inhibition of LEC CaMKIIα⁺ neurons affects fear encoding, fear memory recall, and PPC responses to a conditioned odor. These findings provide direct evidence for the involvement of LEC CaMKIIα⁺ neurons in negative valence encoding.