The organization of feedback projections in a pathway important for processing pheromonal signals.

In most of the mammalian sensory systems there are massive cortical feedback projections to early processing stations. The mammalian accessory olfactory system is considered unique in several aspects. It is specialized for processing pheromonal signals and plays a critical role in regulating sociosexual behaviors. Furthermore, pheromonal signals are believed to bypass cortex and reach the hypothalamic behavioral centers after merely three forward projections. Because the organization of the feedback projections in the accessory olfactory system remains largely unclear, the importance of the feedback projections in the processing of pheromonal signals has been ignored. Here we show that in mice the feedback projections from the bed nucleus of stria terminalis (BST) and the vomeronasal amygdala to the accessory olfactory bulb (AOB) are topographically organized and use different neurotransmitters. By retrograde and anterograde tracing, we find that the feedback projection from the BST terminates in the AOB mitral cell layer, whereas that from the amygdala terminates in the AOB granule cell layer. By combining tracing, genetic labeling of GABAergic neurons, and immunostaining against a marker of glutamatergic synapses, we observe that the BST-to-AOB projection is GABAergic whereas the amygdala-to-AOB projection is glutamatergic. In addition, a substantial number of feedback neurons in the amygdala and BST express estrogen receptors. Thus, the accessory olfactory system, like other sensory systems, possesses extensive feedback projections. Moreover, our results suggest that central hormonal cues may modulate the processing of pheromonal signals at early stations through the precisely organized feedback projections.