Primary dendrites of mitral cells synapse unto neighboring glomeruli independent of their odorant receptor identity.

In the mouse olfactory bulb, neural map topography is largely established by axon-axon interactions of olfactory sensory neurons (OSNs). However, to make the map functional, the OSNs must make proper connections to second-order neurons, the mitral cells. How do the mitral-cell dendrites find their partner glomeruli for synapse formation with OSN axons? Here, we analyze dendrite connections of mitral cells in various mutant mice in which glomerular formation is perturbed. Our present results support the proximity model, whereby mitral cells tend to connect primary dendrites to the nearest neighboring glomeruli regardless of their odorant receptor identities. The physical location of glomeruli rather than the odorant-receptor specificity appears to play a key role in matching mitral cells with their partner OSN axons.

Nrp2 is sufficient to instruct circuit formation of mitral-cells to mediate odour-induced attractive social responses.

Odour information induces various innate responses that are critical to the survival of the individual and for the species. An axon guidance molecule, Neuropilin 2 (Nrp2), is known to mediate targeting of olfactory sensory neurons (primary neurons), to the posteroventral main olfactory bulb (PV MOB) in mice. Here we report that Nrp2-positive (Nrp2+) mitral cells (MCs, second-order neurons) play crucial roles in transmitting attractive social signals from the PV MOB to the anterior part of medial amygdala (MeA). Semaphorin 3F, a repulsive ligand to Nrp2, regulates both migration of Nrp2+ MCs to the PV MOB and their axonal projection to the anterior MeA. In the MC-specific Nrp2 knockout mice, circuit formation of Nrp2+ MCs and odour-induced attractive social responses are impaired. In utero, electroporation demonstrates that activation of the Nrp2 gene in MCs is sufficient to instruct their circuit formation from the PV MOB to the anterior MeA.

Sequential arrival and graded secretion of Sema3F by olfactory neuron axons specify map topography at the bulb.

In the mouse olfactory system, the anatomical locations of olfactory sensory neurons (OSNs) roughly correlate with their axonal projection sites along the dorsal-ventral (D-V) axis of the olfactory bulb (OB). Here we report that an axon guidance receptor, Neuropilin-2 (Nrp2), and its repulsive ligand, Semaphorin-3F (Sema3F), are expressed by OSNs in a complementary manner that is important for establishing olfactory map topography. Sema3F is secreted by early-arriving axons of OSNs and is deposited at the anterodorsal OB to repel Nrp2-positive axons that arrive later. Sequential arrival of OSN axons as well as the graded and complementary expression of Nrp2 and Sema3F by OSNs help to form the topographic order along the D-V axis.