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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Donaldson, Z. R. & Young, L. J. Oxytocin, vasopressin, and the neurogenetics of sociality. Science 322, 900–904 (2008)
Hammock, E. A. D. & Young, L. J. Oxytocin, vasopressin and pair bonding: implications for autism. Phil. Trans. R. Soc. B 361, 2187–2198 (2006)
Frank, E. & Landgraf, R. The vasopressin system–from antidiuresis to psychopathology. Eur. J. Pharmacol. 583, 226–242 (2008)
Ferguson, J. N. et al. Social amnesia in mice lacking the oxytocin gene. Nature Genet. 25, 284–288 (2000)
Brennan, P. A. & Kendrick, K. M. Mammalian social odours: attraction and individual recognition. Phil. Trans. R. Soc. B 361, 2061–2078 (2006)
Winslow, J. T., Hastings, N., Carter, C. S., Harbaugh, C. R. & Insel, T. R. A role for central vasopressin in pair bonding in monogamous prairie voles. Nature 365, 545–548 (1993)
DeVito, L. M. et al. Vasopressin 1b receptor knock-out impairs memory for temporal order. J. Neurosci. 29, 2676–2683 (2009)
Ueta, Y. et al. Transgenic expression of enhanced green fluorescent protein enables direct visualization for physiological studies of vasopressin neurons and isolated nerve terminals of the rat. Endocrinology 146, 406–413 (2005)
Kosaka, K. & Kosaka, T. Synaptic organization of the glomerulus in the main olfactory bulb: compartments of the glomerulus and heterogeneity of the periglomerular cells. Anat. Sci. Int. 80, 80–90 (2005)
Hayar, A., Karnup, S., Ennis, M. & Shipley, M. T. External tufted cells: a major excitatory element that coordinates glomerular activity. J. Neurosci. 24, 6676–6685 (2004)
Brennan, P. A. & Zufall, F. Pheromonal communication in vertebrates. Nature 444, 308–315 (2006)
Ludwig, M. & Leng, G. Dendritic peptide release and peptide-dependent behaviours. Nature Rev. Neurosci. 7, 126–136 (2006)
Ostrowski, N. L., Lolait, S. J. & Young, W. S. Cellular localization of vasopressin V1a receptor messenger ribonucleic acid in adult male rat brain, pineal, and brain vasculature. Endocrinology 135, 1511–1528 (1994)
Gouzènes, L., Desarménien, M. G., Hussy, N., Richard, P. & Moos, F. C. Vasopressin regularizes the phasic firing pattern of rat hypothalamic magnocellular neurons. J. Neurosci. 18, 1879–1885 (1998)
Dluzen, D. E., Muraoka, S., Engelmann, M. & Landgraf, R. The effects of infusion of arginine vasopressin, oxytocin, or their antagonists into the olfactory bulb upon social recognition responses in male rats. Peptides 19, 999–1005 (1998)
Ludwig, M. & Leng, G. Autoinhibition of supraoptic nucleus vasopressin neurons in vivo - a combined retrodialysis/electrophysiological study in rats. Eur. J. Neurosci. 9, 2532–2540 (1997)
Engelmann, M., Wotjak, C. T. & Landgraf, R. Social discrimination procedure: an alternative method to investigate juvenile recognition abilities in rats. Physiol. Behav. 58, 315–321 (1995)
Hassan, A. et al. Small interfering RNA-mediated functional silencing of vasopressin V2 receptors in the mouse kidney. Physiol. Genomics 21, 382–388 (2005)
Saito, M. et al. Diphtheria toxin receptor-mediated conditional and targeted cell ablation in transgenic mice. Nature Biotechnol. 19, 746–750 (2001)
Chen, H., Kohno, K. & Gong, Q. Conditional ablation of mature olfactory sensory neurons mediated by diphtheria toxin receptor. J. Neurocytol. 34, 37–47 (2005)
Jiang, M., Griff, E. R., Ennis, M., Zimmer, L. A. & Shipley, M. T. Activation of locus coeruleus enhances the responses of olfactory bulb mitral cells to weak olfactory nerve input. J. Neurosci. 16, 6319–6329 (1996)
Debarbieux, F., Audinat, E. & Charpak, S. Action potential propagation in dendrites of rat mitral cells in vivo. J. Neurosci. 23, 5553–5560 (2003)
Lévy, F., Kendrick, K. M., Goode, J. A., Guevara-Guzman, R. & Keverne, E. B. Oxytocin and vasopressin release in the olfactory bulb of parturient ewes: changes with maternal experience and effects on acetylcholine, gamma-aminobutyric acid, glutamate and noradrenaline release. Brain Res. 669, 197–206 (1995)
Ludwig, M. et al. Intracellular calcium stores regulate activity-dependent neuropeptide release from dendrites. Nature 418, 85–89 (2002)
Meyer-Lindenberg, A. et al. Genetic variants in AVPR1A linked to autism predict amygdala activation and personality traits in healthy humans. Mol. Psychiatry 14, 968–975 (2000)
Walum, H. et al. Genetic variation in the vasopressin receptor 1a gene (AVPR1A) associates with pair-bonding behavior in humans. Proc. Natl Acad. Sci. USA 105, 14153–14156 (2008)
Ferguson, J. N., Young, L. J. & Insel, T. R. The neuroendocrine basis of social recognition. Front. Neuroendocrinol. 23, 200–224 (2002)
Caldwell, H. K., Lee, H. J., Macbeth, A. H. & Young, W. S. Vasopressin: behavioral roles of an “original” neuropeptide. Prog. Neurobiol. 84, 1–24 (2008)
Bielsky, I. F., Hu, S. B., Ren, X., Terwilliger, E. F. & Young, L. J. The V1a vasopressin receptor is necessary and sufficient for normal social recognition: a gene replacement study. Neuron 47, 503–513 (2005)
Furukawa, N., Saito, M., Hakoshima, T. & Kohno, K. A diphtheria toxin receptor deficient in epidermal growth factor-like biological activity. J. Biochem. 140, 831–841 (2006)
Tobin, V. A. et al. The effects of apelin on the electrical activity of hypothalamic magnocellular vasopressin and oxytocin neurons and somatodendritic peptide release. Endocrinology 149, 6136–6145 (2008)
Orlando, G. F., Langnaese, K., Schulz, C., Wolf, G. & Engelmann, M. Neuronal nitric oxide synthase gene inactivation reduces the expression of vasopressin in the hypothalamic paraventricular nucleus and of catecholamine biosynthetic enzymes in the adrenal gland of the mouse. Stress 11, 42–51 (2008)
Yamamura, Y. et al. OPC-21268, an orally effective, nonpeptide vasopressin V1 receptor antagonist. Science 252, 572–574 (1991)
Ennaceur, A. & Delacour, J. A new one-trial test for neurobiological studies of memory in rats. 1: Behavioral data. Behav. Brain Res. 31, 47–59 (1988)
Ikeda, K. et al. Degeneration of the amygdala/piriform cortex and enhanced fear/anxiety behaviors in sodium pump alpha2 subunit (Atp1a2)-deficient mice. J. Neurosci. 23, 4667–4676 (2003)
Murphy, D. & Wells, S. In vivo gene transfer studies on the regulation and function of the vasopressin and oxytocin genes. J. Neuroendocrinol. 15, 109–125 (2003)
Paxinos, G. & Watson, C. The Rat Brain in Stereotaxic Coordinates 3rd edn (Academic, 1986)
Sabatier, N., Brown, C. H., Ludwig, M. & Leng, G. Phasic spike patterning in rat supraoptic neurones in vivo and in vitro. J. Physiol. (Lond.) 558, 161–180 (2004)
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.
The authors declare no competing financial interests.
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Tobin, V., Hashimoto, H., Wacker, D. et al. An intrinsic vasopressin system in the olfactory bulb is involved in social recognition. Nature 464, 413–417 (2010). https://doi.org/10.1038/nature08826
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