| The mammalian vomeronasal system (VNS) is specialized in the detection of pheromones, chemical signals that modulate social and reproductive behaviors. Here, I studied the molecular receptors involved in the detection of pheromones and the neural circuitry of the VNS.; Candidate pheromone receptors are encoded by two distinct and complex superfamilies of seven-transmembrane domain receptor genes, the V1r and V2r genes, which are expressed selectively in sensory neurons of the vomeronasal organ (VNO). However, there was no functional evidence for a role in mediating pheromone responses. To study the function of V1r genes, I first described the composition of the V1r repertoire. The screening of mouse genomic databases revealed that it comprises ∼140 functional genes which form twelve highly isolated phylogenetic families. Two of these gene families, V1ra and V1rb, which represent ∼12% of the V1r repertoire, are clustered together in a ∼600 kb genomic region. I next employed chromosome engineering technology to delete in the germline of mice the cluster of V1ra-b genes. The mutant mice display deficits in a subset of VNO-dependent behaviors: the expression of male sexual behavior and maternal aggression is substantially altered. Electrophysiologically, the epithelium of their VNO does not respond detectably to specific pheromonal ligands. The behavioral impairment and chemosensory deficits strongly support a pheromone receptor function of V1rs.; The neural circuitry of the accessory olfactory bulb (AOB), the first synaptic relay station of the VNS, provides an anatomical substrate for the coding of pheromone information. Here, I described the axonal projections of vomeronasal sensory neurons (VSN) to the AOB, and the dendritic connectivity pattern of second-order neurons. Genetically traced VSNs expressing a given V2r gene project their axons to 6–10 glomeruli distributed in globally conserved areas of the AOB, a theme similar to V1r-expressing neurons. Surprisingly, second-order neurons tend to project their dendrites to glomeruli innervated by axons of VSNs expressing the same V1r or V2r. Thus, the divergence of sensory axonal projections to the AOB is followed by dendritic convergence of the second-order neurons. Convergence of receptor type information in the olfactory bulb may represent a common design in olfactory systems. |
