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Oxytocin in the Medial Amygdala is Essential for Social Recognition in the Mouse
Open accessAbstract
Oxytocin (OT) knock-out mice fail to recognize familiar conspecifics after repeated social exposures, despite normal olfactory and spatial learning abilities. OT treatment fully restores social recognition. Here we demonstrate that OT acts in the medial amygdala during the initial exposure to facilitate social recognition. OT given before, but not after, the initial encounter restores social recognition in OT knock-out mice. Using c-Fos immunoreactivity (Fos-IR) as a marker of neuronal activation in this initial encounter, we found similar neuronal activation in the wild-type (WT) and OT knock-out mouse in olfactory bulbs, piriform cortex, cortical amygdala, and the lateral septum. Wild-type, but not OT knock-out mice exhibited an induction of Fos-IR in the medial amygdala. Projections sites of the medial amygdala also failed to show a Fos-IR induction in the OT knock-out mice. OT knock-out, but not WT, mice showed dramatic increases in Fos-IR in the somatosensory cortex and the hippocampus, suggesting alternative processing of social cues in these animals. With site-specific injections of OT and an OT antagonist, we demonstrate that OT receptor activation in the medial amygdala is both necessary and sufficient for social recognition in the mouse.
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In the citing paper
“social discrimination is a complex behavior, and several other signaling molecules have been shown to play a role in social discrimination, including oxytocin [35–37] and arginine vasopressin [24, 38–40].”
From Sex-specific effects of neonatal progestin receptor antagonism on juvenile social play behavior in rats (2021) · cites this paper as [36]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“For example, a single treatment with OT 24 hours after birth alters the expression of alloparental behavior in female prairie voles when they reach adulthood [46].”
From Oxytocin and the Neural Mechanisms Regulating Social Cognition and Affiliative Behavior (2009) · cites this paper as [46]
Experimental — accuracy not yet measuredIn the citing paper
“OTR mouse knockouts show social recognition deficits that can be remediated by oxytocin injections in the medial amygdala [163].”
From Consensus Paper: Pathological Role of the Cerebellum in Autism (2012) · cites this paper as [163]
In the citing paper
“and infusions of an OXTR antagonist into the MeA of wild-type mice recapitulates those deficits in social memory (24).”
From Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications (2016) · cites this paper as [24]
In the citing paper
“Infusions of OT directly into the medial amygdala (MeA) of OT knockout mice rescues the social amnesia described above”
From Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications (2016) · cites this paper as [24]
In the citing paper
“For example, in the studies in mice that demonstrated the requirement of OT in the MeA for social memory of a familiar conspecific, social memory was measured by the habituation of time spent in olfactory exploration of the stimulus animal after repeated presentations (8,24).”
From Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications (2016) · cites this paper as [24]
In the citing paper
“Mice lacking the OT gene have impaired social memory that can be recovered by OT treatment prior to the initial social encounter, demonstrating that the presence of OT at the time of the salient event is necessary and sufficient for social memory (Ferguson et al 2000; Ferguson et al 2001).”
From The behavioral, anatomical and pharmacological parallels between social attachment, love and addiction (2012) · cites this paper as Ferguson et al 2001
In the citing paper
“Utilizing the three-chamber social memory assay in rodents, it was found that OXT activity in the septum and amygdala is required for social memory [43,70].”
From Neural circuits regulating prosocial behaviors (2023) · cites this paper as [43]
In the citing paper
“For example, mice with impairments in either system show deficits in distinguishing between familiar and novel conspecifics (74,94,95).”
From Oxytocin, Vasopressin, and Social Behavior: From Neural Circuits to Clinical Opportunities (2022) · cites this paper as [74]
In the citing paper
“OXTRs in the MeA receive OXT input from the PVN that help discriminate between sexand individual cues (53,74,96).”
From Oxytocin, Vasopressin, and Social Behavior: From Neural Circuits to Clinical Opportunities (2022) · cites this paper as [74]
In the citing paper
“OXT is released within the brain as relationships form and it facilitates experience-dependent social adaptations including the formation of social memories 14,15, the establishment of mating-induced pair bonds 2 and maternal responsiveness 16.”
From Social experience alters oxytocinergic modulation in the nucleus accumbens of female prairie voles (2022) · cites this paper as [14]
In the citing paper
“In a subsequent study (Ferguson et al. 2001), we found that OT acts in the medial amygdala during initial exposure to other conspecifics to facilitate social recognition.”
From A precision medicine approach to oxytocin trials (2017) · cites this paper as Ferguson et al. 2001
In the citing paper
“Oxytocin knockout mice also exhibit social recognition impairments, however, these impairments can be reversed by oxytocin infusion into medial amygdala, indicating special involvement of the amygdala in this process (Choleris et al., 2003, Ferguson et al., 2001, Ferguson et al., 2000).”
From Oxytocin, motivation and the role of dopamine (2014) · cites this paper as Ferguson et al., 2001
In the citing paper
“The neuropeptide oxytocin (OT) is implicated in the modulation of many social responses (Ross and Young, 2009; Insel and Hulihan, 1995; Ferguson et al., 2001; Dölen et al., 2013).”
From Neuronal Representation of Social Information in the Medial Amygdala of Awake Behaving Mice (2017) · cites this paper as Ferguson et al., 2001
In the citing paper
“Considering the expression of OXTR in the MeApd, and its role in social and sexual recognition (Ferguson et al., 2001; Yao et al., 2017), plasticity may be also directly derived from the regulation of local circuitry in the MeA.”
From Neuronal Representation of Social Information in the Medial Amygdala of Awake Behaving Mice (2017) · cites this paper as Ferguson et al., 2001
In the citing paper
“Intranasal oxytocin is also known to enhance prosocial and affiliative behaviors in rodents (Ferguson et al., 2001; Witt et al., 1992) and non-human primates (Chang and Platt, 2013).”
From Effects of adverse childhood experiences on the association between intranasal oxytocin and social stress reactivity among individuals with cocaine dependence (2015) · cites this paper as Ferguson et al., 2001
In the citing paper
“Other studies, however, have suggested that the neuropeptide oxytocin can specifically affect social behaviors, which would suggest separable mechanisms at the pharmacological level.”
From Oxytocin decreases aversion to angry faces in an associative learning task (2010) · cites this paper as Ferguson et al., 2001
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Metadata
- Authors
- Ferguson, J. N., Aldag, J. M., Insel, T. R., & Young, L. J.
- Affiliations
- Emory University (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2001-10-15
- Volume
- 21
- Issue
- 20
- Pages
- 8278-8285
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6763861
- OpenAlex
- W2164671673
- Cited by
- 1,043
- References
- 56
- Citations by year
- 2026: 20 · 2025: 20 · 2024: 29 · 2023: 43 · 2022: 46 · 2021: 61 · 2020: 30 · 2019: 37 · 2018: 63 · 2017: 48 · 2016: 61 · 2015: 78 · 2014: 53 · 2013: 53 · 2012: 59
- FWCI
- 38.87
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation (9876754)
- National Institute of Mental Health (R29MH056897, MH 56897, R01MH056897)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Sensory Systems › Olfactory and Sensory Function Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- oxytocin, medial amygdala, social recognition, oxytocin receptor, c-Fos neuronal activation, olfactory bulb, piriform cortex, cortical amygdala, lateral septum, somatosensory cortex, hippocampus, social behavior
- MeSH terms
- Amygdala, Animals, Behavior, Animal, Dose-Response Relationship, Drug, Female, Immunohistochemistry, Injections, Intraventricular, Male, Mice, Inbred Strains, Olfactory Bulb, Ovariectomy, Oxytocin, Smell, Social Behavior, Proto-Oncogene Proteins c-fos, Mice, Knockout, Recognition, Psychology, Mice
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