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Archival Report| Volume 76, ISSUE 5, P377-386, September 01, 2014

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Long-Term Social Recognition Memory Is Mediated by Oxytocin-Dependent Synaptic Plasticity in the Medial Amygdala

      Background

      Recognition of specific individuals is fundamental to mammalian social behavior and is mediated in most mammals by the main and accessory olfactory systems. Both these systems innervate the medial amygdala (MeA), where activity of the neuropeptide oxytocin is thought to mediate social recognition memory (SRM). The specific contribution of the MeA to SRM formation and the specific actions of oxytocin in the MeA are unknown.

      Methods

      We used the social discrimination test to evaluate short-term and long-term SRM in adult Sprague-Dawley male rats (n = 38). The role of protein synthesis in the MeA was investigated by local application of the protein synthesis blocker anisomycin (n = 11). Synaptic plasticity was assessed in vivo by recording the MeA evoked field potential responses to stimulation of the main (n = 21) and accessory (n = 56) olfactory bulbs before and after theta burst stimulation. Intracerebroventricular administration of saline, oxytocin, or oxytocin receptor antagonist was used to measure the effect of oxytocin on synaptic plasticity.

      Results

      Anisomycin application to the MeA prevented the formation of long-term SRM. In addition, the responses of MeA neurons underwent long-term depression (LTD) after theta burst stimulation of the accessory olfactory bulb, but not the main accessory bulb, in an oxytocin-dependent manner. No LTD was found in socially isolated rats, which are known to lack long-term SRM. Finally, accessory olfactory bulb stimulation before SRM acquisition blocked long-term SRM, supporting the involvement of LTD in the MeA in formation of long-term SRM.

      Conclusions

      Our results indicate that long-term SRM in rats involves protein synthesis and oxytocin-dependent LTD in the MeA.

      Key Words

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      References

        • Gheusi G.
        • Bluthe R.M.
        • Goodall G.
        • Dantzer R.
        Social and individual recognition in rodents: Methodological aspects and neurobiological bases.
        Behavioural Processes. 1994; 33: 59-88
        • Insel T.R.
        • Fernald R.D.
        How the brain processes social information: Searching for the social brain.
        Annu Rev Neurosci. 2004; 27: 697-722
        • Dulac C.
        • Torello A.T.
        Molecular detection of pheromone signals in mammals: From genes to behaviour.
        Nat Rev Neurosci. 2003; 4: 551-562
        • Bielsky I.F.
        • Young L.J.
        Oxytocin, vasopressin, and social recognition in mammals.
        Peptides. 2004; 25: 1565-1574
        • Ferguson J.N.
        • Young L.J.
        • Insel T.R.
        The neuroendocrine basis of social recognition.
        Front Neuroendocrinol. 2002; 23: 200-224
        • Thor D.H.
        • Holloway W.R.
        Social memory of the male laboratory rat.
        J Comp Physiol Psychol. 1982; 96: 1000-1006
        • Kogan J.H.
        • Frankland P.W.
        • Silva A.J.
        Long-term memory underlying hippocampus-dependent social recognition in mice.
        Hippocampus. 2000; 10: 47-56
        • Shahar-Gold H.
        • Gur R.
        • Wagner S.
        Rapid and reversible impairments of short- and long-term social recognition memory are caused by acute isolation of adult rats via distinct mechanisms.
        PLoS One. 2013; 8: e65085
        • Bailey C.H.
        • Bartsch D.
        • Kandel E.R.
        Toward a molecular definition of long-term memory storage.
        Proc Natl Acad Sci U S A. 1996; 93: 13445-13452
        • Mayford M.
        • Siegelbaum S.A.
        • Kandel E.R.
        Synapses and memory storage.
        Cold Spring Harb Perspect Biol. 2012; 4: a005751
        • Luscher C.
        • Malenka R.C.
        NMDA receptor-dependent long-term potentiation and long-term depression (LTP/LTD).
        Cold Spring Harb Perspect Biol. 2012; 4: a005710
        • Lee H.J.
        • Macbeth A.H.
        • Pagani J.H.
        • Young 3rd, W.S.
        Oxytocin: The great facilitator of life.
        Prog Neurobiol. 2009; 88: 127-151
        • Harony H.
        • Wagner S.
        The contribution of oxytocin and vasopressin to mammalian social behavior: Potential role in autism spectrum disorder.
        Neurosignals. 2010; 18: 82-97
        • Gimpl G.
        • Fahrenholz F.
        The oxytocin receptor system: Structure, function, and regulation.
        Physiol Rev. 2001; 81: 629-683
        • Ferguson J.N.
        • Aldag J.M.
        • Insel T.R.
        • Young L.J.
        Oxytocin in the medial amygdala is essential for social recognition in the mouse.
        J Neurosci. 2001; 21: 8278-8285
        • Lukas M.
        • Toth I.
        • Veenema A.H.
        • Neumann I.D.
        Oxytocin mediates rodent social memory within the lateral septum and the medial amygdala depending on the relevance of the social stimulus: Male juvenile versus female adult conspecifics.
        Psychoneuroendocrinology. 2013; 38: 916-926
        • Saar D.
        • Grossman Y.
        • Barkai E.
        Reduced after-hyperpolarization in rat piriform cortex pyramidal neurons is associated with increased learning capability during operant conditioning.
        Eur J Neurosci. 1998; 10: 1518-1523
      1. Paxinos G, Watson C (2007): The Rat Brain in Stereotxic Coordinates, 6th ed. Waltham, MA: Academic Press.

        • Engelmann M.
        • Wotjak C.T.
        • Landgraf R.
        Social discrimination procedure: An alternative method to investigate juvenile recognition abilities in rats.
        Physiol Behav. 1995; 58: 315-321
        • Mouly A.M.
        • Di Scala G.
        Entorhinal cortex stimulation modulates amygdala and piriform cortex responses to olfactory bulb inputs in the rat.
        Neuroscience. 2006; 137: 1131-1141
        • Hess G.
        • Aizenman C.D.
        • Donoghue J.P.
        Conditions for the induction of long-term potentiation in layer II/III horizontal connections of the rat motor cortex.
        J Neurophysiol. 1996; 75: 1765-1778
        • Kappeler P.M.
        • Barrett L.
        • Blumstein D.T.
        • Clutton-Brock T.H.
        Constraints and flexibility in mammalian social behaviour: Introduction and synthesis.
        Philos Trans R Soc Lond B Biol Sci. 2013; 368: 20120337
        • Goodson J.L.
        • Kabelik D.
        Dynamic limbic networks and social diversity in vertebrates: from neural context to neuromodulatory patterning.
        Front Neuroendocrinol. 2009; 30: 429-441
        • Goodson J.L.
        Deconstructing sociality, social evolution and relevant nonapeptide functions.
        Psychoneuroendocrinology. 2013; 38: 465-478
        • Young L.J.
        Frank A. Beach Award. Oxytocin and vasopressin receptors and species-typical social behaviors.
        Horm Behav. 1999; 36: 212-221
        • Pro-Sistiaga P.
        • Mohedano-Moriano A.
        • Ubeda-Banon I.
        • Del Mar Arroyo-Jimenez M.
        • Marcos P.
        • Artacho-Perula E.
        • et al.
        Convergence of olfactory and vomeronasal projections in the rat basal telencephalon.
        J Comp Neurol. 2007; 504: 346-362
        • Isogai Y.
        • Si S.
        • Pont-Lezica L.
        • Tan T.
        • Kapoor V.
        • Murthy V.N.
        • et al.
        Molecular organization of vomeronasal chemoreception.
        Nature. 2011; 478: 241-245
        • Levy F.
        • Keller M.
        • Poindron P.
        Olfactory regulation of maternal behavior in mammals.
        Horm Behav. 2004; 46: 284-302
        • Tachikawa K.S.
        • Yoshihara Y.
        • Kuroda K.O.
        Behavioral transition from attack to parenting in male mice: A crucial role of the vomeronasal system.
        J Neurosci. 2013; 33: 5120-5126
        • Brennan P.A.
        The nose knows who’s who: Chemosensory individuality and mate recognition in mice.
        Horm Behav. 2004; 46: 231-240
        • Neumann I.D
        Brain oxytocin: A key regulator of emotional and social behaviours in both females and males.
        J Neuroendocrinol. 2008; 20: 858-865
        • Leng G.
        • Meddle S.L.
        • Douglas A.J.
        Oxytocin and the maternal brain.
        Curr Opin Pharmacol. 2008; 8: 731-734
        • Choleris E.
        • Little S.R.
        • Mong J.A.
        • Puram S.V.
        • Langer R.
        • Pfaff D.W.
        Microparticle-based delivery of oxytocin receptor antisense DNA in the medial amygdala blocks social recognition in female mice.
        Proc Natl Acad Sci U S A. 2007; 104: 4670-4675
        • Lin Y.T.
        • Huang C.C.
        • Hsu K.S.
        Oxytocin promotes long-term potentiation by enhancing epidermal growth factor receptor-mediated local translation of protein kinase Mzeta.
        J Neurosci. 2012; 32: 15476-15488
        • Tomizawa K.
        • Iga N.
        • Lu Y.F.
        • Moriwaki A.
        • Matsushita M.
        • Li S.T.
        • et al.
        Oxytocin improves long-lasting spatial memory during motherhood through MAP kinase cascade.
        Nat Neurosci. 2003; 6: 384-390
        • Fang L.Y.
        • Quan R.D.
        • Kaba H.
        Oxytocin facilitates the induction of long-term potentiation in the accessory olfactory bulb.
        Neurosci Lett. 2008; 438: 133-137
        • Dubrovsky B.
        • Harris J.
        • Gijsbers K.
        • Tatarinov A.
        Oxytocin induces long-term depression on the rat dentate gyrus: Possible ATPase and ectoprotein kinase mediation.
        Brain Res Bull. 2002; 58: 141-147
        • Neumann I.D.
        • Maloumby R.
        • Beiderbeck D.I.
        • Lukas M.
        • Landgraf R.
        Increased brain and plasma oxytocin after nasal and peripheral administration in rats and mice.
        Psychoneuroendocrinology. 2013; 38: 1985-1993
        • Stevenson R.J.
        An initial evaluation of the functions of human olfaction.
        Chem Senses. 2010; 35: 3-20
        • Wysocki C.J.
        • Preti G.
        Facts, fallacies, fears, and frustrations with human pheromones.
        Anat Rec A Discov Mol Cell Evol Biol. 2004; 281: 1201-1211
        • Sokolowski K.
        • Corbin J.G.
        Wired for behaviors: From development to function of innate limbic system circuitry.
        Front Mol Neurosci. 2012; 5: 55
        • Adolphs R.
        What does the amygdala contribute to social cognition?.
        Ann N Y Acad Sci. 2010; 1191: 42-61
        • Baumgartner T.
        • Heinrichs M.
        • Vonlanthen A.
        • Fischbacher U.
        • Fehr E.
        Oxytocin shapes the neural circuitry of trust and trust adaptation in humans.
        Neuron. 2008; 58: 639-650
        • Domes G.
        • Heinrichs M.
        • Glascher J.
        • Buchel C.
        • Braus D.F.
        • Herpertz S.C.
        Oxytocin attenuates amygdala responses to emotional faces regardless of valence.
        Biol Psychiatry. 2007; 62: 1187-1190
        • Gamer M.
        • Zurowski B.
        • Buchel C.
        Different amygdala subregions mediate valence-related and attentional effects of oxytocin in humans.
        Proc Natl Acad Sci U S A. 2010; 107: 9400-9405
        • Kirsch P.
        • Esslinger C.
        • Chen Q.
        • Mier D.
        • Lis S.
        • Siddhanti S.
        • et al.
        Oxytocin modulates neural circuitry for social cognition and fear in humans.
        J Neurosci. 2005; 25: 11489-11493
        • Petrovic P.
        • Kalisch R.
        • Singer T.
        • Dolan R.J.
        Oxytocin attenuates affective evaluations of conditioned faces and amygdala activity.
        J Neurosci. 2008; 28: 6607-6615
        • Riem M.M.
        • Bakermans-Kranenburg M.J.
        • Pieper S.
        • Tops M.
        • Boksem M.A.
        • Vermeiren R.R.
        • et al.
        Oxytocin modulates amygdala, insula, and inferior frontal gyrus responses to infant crying: A randomized controlled trial.
        Biol Psychiatry. 2011; 70: 291-297
        • Striepens N.
        • Scheele D.
        • Kendrick K.M.
        • Becker B.
        • Schafer L.
        • Schwalba K.
        • et al.
        Oxytocin facilitates protective responses to aversive social stimuli in males.
        Proc Natl Acad Sci U S A. 2012; 109: 18144-18149
        • Kanat M.
        • Heinrichs M.
        • Domes G.
        Oxytocin and the social brain: Neural mechanisms and perspectives in human research [published online ahead of print Nov 8].
        Brain Res. 2013;

      Linked Article

      • Amygdala, Oxytocin, and Social Cognition in Autism Spectrum Disorders
        Biological PsychiatryVol. 76Issue 5
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          In the past decade, the elaboration of animal models has brought significant advances in understanding the development of the limbic neural circuitry and the modulatory role of hormones and neuropeptides in complex behaviors, such as social cognition. The study of Gur et al. (1) in this issue of Biological Psychiatry yields important and exciting results elucidating the molecular mechanism by which oxytocin (OT) enhances social recognition memory (SRM) in adult Sprague-Dawley male rats. In rodents, the acquisition of information about conspecifics is mediated by olfactory and pheromonal signals, conveyed via the main olfactory bulb and the accessory olfactory bulb (AOB), both projecting to the medial amygdala (MeA).
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