An intrinsic vasopressin system in the olfactory bulb is involved in social recognition

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Abstract

Many peptides, when released as chemical messengers within the brain, have powerful influences on complex behaviours. Most strikingly, vasopressin and oxytocin, once thought of as circulating hormones whose actions were confined to peripheral organs, are now known to be released in the brain, where they have fundamentally important roles in social behaviours1. In humans, disruptions of these peptide systems have been linked to several neurobehavioural disorders, including Prader–Willi syndrome, affective disorders and obsessive–compulsive disorder, and polymorphisms of V1a vasopressin receptor have been linked to autism2,3. Here we report that the rat olfactory bulb contains a large population of interneurons which express vasopressin, that blocking the actions of vasopressin in the olfactory bulb impairs the social recognition abilities of rats and that vasopressin agonists and antagonists can modulate the processing of information by olfactory bulb neurons. The findings indicate that social information is processed in part by a vasopressin system intrinsic to the olfactory system.

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Figure 1: Vasopressin neurons in the olfactory bulb.
Figure 2: Effects of V1a receptor blockade and vasopressin cell destruction on social recognition.
Figure 3: Specificity of effects on social recognition.
Figure 4: Vasopressin effects on mitral cells.

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Acknowledgements

We thank V. Bishop, T. Gillespie, K. Richter and R. Murau for technical support; E. Mohr for vectors containing the total vasopressin sequence and a partial sequence; H. Gainer for vasopressin and oxytocin antibodies; Y. Ueta for the vasopressin–eGFP transgenic rats; K. Kohno and E. Kobayashi for the complementary DNA for the diphtheria toxin receptor and support for the production of transgenic rats, respectively; and D. Murphy for the DNA for the vasopressin promoter. This work was supported by grants from the Biotechnology and Biological Sciences Research Council (M.L., S.L.M.), the Japan Ministry of Education, Culture, Sports, Science and Technology (T.O., Y.T.), the Deutsche Forschungsgemeinschaft (M.E., J.N.) and the German Academic Exchange Service/Academic Research Collaboration (M.L., M.E.), and by a fellowship from the Japan Society for the Promotion of Science awarded to H.H.

Author Contributions M.L., G.L., S.L.M. and M.E. designed the experiments. V.A.T. performed the immunohistochemistry and in vitro electrophysiology (Fig. 1). D.W.W., S.L.M. and C.C. performed tracer injections (Fig. 1m–o). M.E. and J.N. performed the receptor antagonist and siRNA study with behavioural analysis (Figs 2b, c and 3 and Supplementary Figs 1 and 2a, b). Y.T. and T.O. produced diphtheria toxin receptor transgenic rats and performed behaviour experiments (Figs 2d and 3c and Supplementary Fig. 2d–i). K.L. performed in situ hybridization and R.L. performed the vasopressin radioimmune assay. H.H. performed in vivo electrophysiology (Fig. 4 and Supplementary Fig. 3). M.L., M.E., T.O., G.L. and H.H. performed general data processing and statistical analyses. M.L. and G.L. wrote the paper.

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Correspondence to Mike Ludwig.

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