Distinct projection patterns of different classes of layer 2 principal neurons in the olfactory cortex

The broadly-distributed, non-topographic projections to and from the olfactory cortex may suggest a flat, non-hierarchical organization in odor information processing. Layer 2 principal neurons in the anterior piriform cortex (APC) can be divided into 2 subtypes: semilunar (SL) and superficial pyramidal (SP) cells. Although it is known that SL and SP cells receive differential inputs from the olfactory bulb (OB), little is known about their projections to other olfactory regions. Here, we examined axonal projections of SL and SP cells using a combination of mouse genetics and retrograde labeling. Retrograde tracing from the OB or posterior piriform cortex (PPC) showed that the APC projects to these brain regions mainly through layer 2b cells, and dual-labeling revealed many cells extending collaterals to both target regions. Furthermore, a transgenic mouse line specifically labeling SL cells showed that they send profuse axonal projections to olfactory cortical areas, but not to the OB. These findings support a model in which information flow from SL to SP cells and back to the OB is mediated by a hierarchical feedback circuit, whereas both SL and SP cells broadcast information to higher olfactory areas in a parallel manner.