Anterior olfactory cortices differentially transform bottom-up odor signals to produce inverse top-down outputs

Odor information arrives first in the main olfactory bulb and is then broadcasted to the olfactory cortices and striatum. Downstream regions have unique cellular and connectivity architectures that may generate different coding patterns to the same odors. To reveal region-specific response features, tuning and decoding of single-unit populations, we recorded responses to the same odors under the same conditions across regions, namely the main olfactory bulb (MOB), the anterior olfactory nucleus (AON), the anterior piriform cortex (aPC), and the olfactory tubercle of the ventral striatum (OT), of awake male mice. We focused on chemically closely related aldehydes that still create distinct percepts. The MOB had the highest decoding accuracy for aldehydes and was the only region encoding chemical similarity. The MOB had the highest fraction of inhibited responses and narrowly tuned odor-excited responses in terms of timing and odor selectivity. Downstream, the interconnected AON and aPC differed in their response patterns to the same stimuli. While odor-excited responses dominated the AON, the aPC had a comparably high fraction of odor-inhibited responses. Both cortices share a main output target that is the MOB. This prompted us to test if the two regions convey also different net outputs. Aldehydes activated AON terminals in the MOB as a bulk signal, but inhibited those from the aPC. The differential cortical projection responses generalized to complex odors. In summary, olfactory regions reveal specialized features in their encoding with AON and aPC differing in their local computations thereby generating inverse net centrifugal and inter-cortical outputs. Significance statement Odor signals are first computed in the olfactory bulb and then distributed in parallel streams to downstream interconnected cortices. The functional specializations of these downstream regions are only partially understood. We therefore probed how the representations of the same stimuli differ in downstream regions. The olfactory bulb produces a highly discriminating and inhibition-excitation balanced odor coding that transforms into distributed odor representations in the olfactory cortices. The two anterior olfactory cortices however differ, surprisingly, with the anterior piriform cortex producing a net inhibited top-down output activity back to the olfactory bulb, while the anterior olfactory nucleus output is consistently excited. These opposing cortical outputs generalize to complex natural odors and reveal unexpected functional differentiations of primary olfactory cortices.