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

Kasumi Inokuchi,Haruhiko Bito,Hitoshi Sakano,Fumiaki Imamura,Haruki Takeuchi,Takefumi Kikusui,Ryang Kim,Hirofumi Nishizumi,Hiroyuki Okuno

doi:10.1038/ncomms15977

Kasumi Inokuchi, Haruhiko Bito + Show 7 more

Open Access

https://doi.org/10.1038/ncomms15977

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Abstract

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.

Highlights

Odour information induces various innate responses that are critical to the survival of the individual and for the species
How is it that the map information is transmitted from the olfactory bulb (OB) to the olfactory cortex (OC) for behavioural decisions? For olfactory map formation, olfactory sensory neurons (OSNs) axons are guided to approximate locations in the OB by using different sets of axon guidance molecules[8,9,10,11] and the map is further refined in an activity-dependent manner[12]
We have previously reported that Nrp[2] þ OSN axons are guided from the ventral olfactory epithelium (OE) to the posteroventral main olfactory bulb (PV main OB (MOB)) by repulsive interactions with Semaphorin 3F (Sema3F) secreted by dorsal OSN axons[11]

Summary

Introduction

Odour information induces various innate responses that are critical to the survival of the individual and for the species. Some attraction behaviours mediated by the MeA are not affected in the knockout (KO) of TrpC2 (AOB-specific ion channel)[24,25,26], but impaired in the KO of CNG-A2 (MOB-specific ion channel)[27] These previous experiments indicate that the main olfactory system plays a critical role in inducing attractive social responses, the exact mechanism for how odour signals are correctly transmitted from the MOB to the MeA remains uncertain. It is unclear whether the second-order neurons, M/T cells, can be divided into different subsets for specific roles and how their cell lineages are determined during development. In utero, electroporation demonstrates that activation of the Nrp[2] gene in MCs is sufficient to instruct circuit formation from the PV MOB to the anterior MeA

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Conclusion