Oxytocin, Neural Plasticity, and Social Behavior.

Oxytocin regulates parturition, lactation, parental nurturing, and many other social behaviors in both sexes. The circuit mechanisms by which oxytocin modulates social behavior are receiving increasing attention. Here, we review recent studies on oxytocin modulation of neural circuit function and social behavior, largely enabled by new methods of monitoring and manipulating oxytocin or oxytocin receptor neurons in vivo. These studies indicate that oxytocin can enhance the salience of social stimuli and increase signal-to-noise ratios by modulating spiking and synaptic plasticity in the context of circuits and networks. We highlight oxytocin effects on social behavior in nontraditional organisms such as prairie voles and discuss opportunities to enhance the utility of these organisms for studying circuit-level modulation of social behaviors. We then discuss recent insights into oxytocin neuron activity during social interactions. We conclude by discussing some of the major questions and opportunities in the field ahead. Expected final online publication date for the Annual Review of Neuroscience, Volume 44 is July 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

• Publication year

  2021

• Venue

  Annual Review of Neuroscience

• Publication date

  2021-04-06

• Fields of study

  Biology, Medicine, Psychology

• Identifiers
  DOI 10.1146/annurev-neuro-102320-102847PMID 33823654PMCID PMC8604207
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Universal nomenclature for oxytocin–vasotocin ligand and receptor families

  2021cited by this paper
• Oxytocin, vasopressin and social behavior in the age of genome editing: A comparative perspective.

  2020cited by this paper
• Heterosynaptic Plasticity Determines the Set Point for Cortical Excitatory-Inhibitory Balance.

  2020cited by this paper
• Rescue of oxytocin response and social behavior in a rodent model of autism

  2020cited by this paper
• Innate and plastic mechanisms for maternal behaviour in auditory cortex

  2020cited by this paper
• Oxytocin and Sensory Network Plasticity

  2020cited by this paper
• Social Stimuli Induce Activation of Oxytocin Neurons Within the Paraventricular Nucleus of the Hypothalamus to Promote Social Behavior in Male Mice

  2020cited by this paper
• Investigation of Oxtr-expressing Neurons Projecting to Nucleus Accumbens using Oxtr-ires-Cre Knock-in prairie Voles (Microtus ochrogaster).

  2020cited by this paper
• Sexually dimorphic role of oxytocin in medaka mate choice

  2020cited by this paper
• Coding of social novelty in the hippocampal CA2 region and its disruption and rescue in a 22q11.2 microdeletion mouse model

  2020cited by this paper
• Translational opportunities for circuit-based social neuroscience: advancing 21st century psychiatry.

  2020cited by this paper
• Innate and plastic mechanisms in auditory cortex for maternal behavior

  2020cited by this paper
• Oxytocin selectively excites interneurons and inhibits output neurons of the bed nucleus of the stria terminalis (BNST)

  2020cited by this paper
• Parallel social information processing circuits are differentially impacted in autism

  2020cited by this paper
• Reconstruction of the Hypothalamo-Neurohypophysial System and Functional Dissection of Magnocellular Oxytocin Neurons in the Brain

  2020cited by this paper
• Social touch promotes interfemale communication via activation of parvocellular oxytocin neurons

  2020cited by this paper
• Inducing Partner Preference in Mice by Chemogenetic Stimulation of CA2 Hippocampal Subfield

  2020cited by this paper
• Oxytocin signals via Gi and Gq to drive persistent CA2 pyramidal cell firing and strengthen CA3-CA1 neurotransmission

  2020cited by this paper
• Wireless Optogenetic Stimulation of Oxytocin Neurons in a Semi-natural Setup Dynamically Elevates Both Pro-social and Agonistic Behaviors

  2020cited by this paper
• Development of a genetically-encoded oxytocin sensor

  2020cited by this paper
• Quantitative cellular-resolution map of the oxytocin receptor in postnatally developing mouse brains

  2019cited by this paper
• Regulation of synaptic plasticity in hippocampal area CA2.

  2019cited by this paper
• Coding of social novelty in the hippocampal CA2 region and its disruption and rescue in a mouse model of schizophrenia

  2019cited by this paper
• Oxytocin neurons enable social transmission of maternal behaviour

  2019influential reference
• Oxytocin increases inhibitory synaptic transmission and blocks the development of long-term potentiation in the lateral amygdala.

  2019cited by this paper
• Single-cell transcriptomic evidence for dense intracortical neuropeptide networks

  2019cited by this paper
• Circuits for social learning: A unified model and application to Autism Spectrum Disorder.

  2019cited by this paper
• The inflammatory event of birth: How oxytocin signaling may guide the development of the brain and gastrointestinal system.

  2019cited by this paper
• Oxytocin Signaling in the Central Amygdala Modulates Emotion Discrimination in Mice.

  2019cited by this paper
• Increased anxiety and decreased sociability induced by paternal deprivation involve the PVN-PrL OTergic pathway

  2019cited by this paper
• Oxytocin Increases Phasic and Tonic GABAergic Transmission in CA1 Region of Mouse Hippocampus

  2019cited by this paper
• G protein-assisted optimization of GPCR-activation based (GRAB) sensors

  2019cited by this paper
• Oxytocin-dependent reopening of a social reward learning critical period with MDMA

  2019cited by this paper
• Oxytocin receptor knockout prairie voles generated by CRISPR/Cas9 editing show reduced preference for social novelty and exaggerated repetitive behaviors.

  2019cited by this paper
• Thalamic integration of social stimuli regulating parental behavior and the oxytocin system.

  2018cited by this paper
• The Oxytocin Receptor: From Intracellular Signaling to Behavior.

  2018cited by this paper
• A hippocampal CA2 to lateral septal circuit disinhibits social aggression

  2018cited by this paper
• Oxytocin as a Modulator of Synaptic Plasticity: Implications for Neurodevelopmental Disorders

  2018cited by this paper
• Molecular Mechanisms of Oxytocin Signaling at the Synaptic Connection

  2018cited by this paper
• Oxytocin Transforms Firing Mode of CA2 Hippocampal Neurons.

  2018influential reference
• The neural mechanisms and circuitry of the pair bond

  2018cited by this paper
• Neuromodulation of maternal circuits by oxytocin

  2018cited by this paper
• Corticoamygdala Transfer of Socially Derived Information Gates Observational Learning.

  2018cited by this paper
• DeepLabCut: markerless pose estimation of user-defined body parts with deep learning

  2018cited by this paper
• Oxytocin functions as a spatiotemporal filter for excitatory synaptic inputs to VTA dopamine neurons

  2018cited by this paper
• Oxytocin and Animal Models for Autism Spectrum Disorder.

  2018cited by this paper
• Hippocampal oxytocin receptors are necessary for discrimination of social stimuli

  2017cited by this paper
• Oxytocin receptor dynamics in the brain across development and species

  2017cited by this paper
• Freezing suppression by oxytocin in central amygdala allows alternate defensive behaviours and mother-pup interactions

  2017cited by this paper
• Oxytocin receptors modulate a social salience neural network in male prairie voles

  2017cited by this paper
• Insular Cortex Mediates Approach and Avoidance Responses to Social Affective Stimuli

  2017influential reference
• Biased Oxytocinergic Modulation of Midbrain Dopamine Systems.

  2017cited by this paper
• Oxytocin and vasopressin neural networks: Implications for social behavioral diversity and translational neuroscience

  2017cited by this paper
• Oxytocin improves behavioral and electrophysiological deficits in a novel Shank3-deficient rat

  2017cited by this paper
• Dynamic corticostriatal activity biases social bonding in monogamous female prairie voles

  2017cited by this paper
• Gating of social reward by oxytocin in the ventral tegmental area

  2017cited by this paper
• Oxytocin signaling in the medial amygdala is required for sex discrimination of social cues

  2017cited by this paper
• Conditional Deletion of Hippocampal CA2/CA3a Oxytocin Receptors Impairs the Persistence of Long-Term Social Recognition Memory in Mice

  2017cited by this paper
• The genetic basis of parental care evolution in monogamous mice

  2017cited by this paper
• Cross-talk among oxytocin and arginine-vasopressin receptors: Relevance for basic and clinical studies of the brain and periphery.

  2017cited by this paper
• Neuronal Representation of Social Information in the Medial Amygdala of Awake Behaving Mice.

  2017cited by this paper
• Neural mechanisms of mother-infant bonding and pair bonding: Similarities, differences, and broader implications.

  2016cited by this paper
• Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications

  2016cited by this paper
• Variation in the Oxytocin Receptor Gene Predicts Brain Region-Specific Expression and Social Attachment.

  2016cited by this paper
• Central oxytocin receptors mediate mating-induced partner preferences and enhance correlated activation across forebrain nuclei in male prairie voles.

  2016cited by this paper
• Oxytocin depolarizes fast‐spiking hilar interneurons and induces GABA release onto mossy cells of the rat dentate gyrus

  2016cited by this paper
• Oxytocin Enhances Social Recognition by Modulating Cortical Control of Early Olfactory Processing.

  2016cited by this paper
• A Distributed Network for Social Cognition Enriched for Oxytocin Receptors

  2016influential reference
• A Cortical Circuit for Sexually Dimorphic Oxytocin-Dependent Anxiety Behaviors.

  2016cited by this paper
• Mate-guarding behavior enhances male reproductive success via familiarization with mating partners in medaka fish

  2016cited by this paper
• Oxytocin in the nucleus accumbens shell reverses CRFR2-evoked passive stress-coping after partner loss in monogamous male prairie voles.

  2016cited by this paper
• Oxytocin-dependent consolation behavior in rodents

  2016cited by this paper
• Faculty Opinions recommendation of A new population of parvocellular oxytocin neurons controlling magnocellular neuron activity and inflammatory pain processing.

  2016cited by this paper
• Melanocortin Receptor Agonists Facilitate Oxytocin-Dependent Partner Preference Formation in the Prairie Vole

  2015cited by this paper
• Can oxytocin treat autism?

  2015cited by this paper
• Plasticity of cortical excitatory-inhibitory balance.

  2015cited by this paper
• Exogenous and evoked oxytocin restores social behavior in the Cntnap2 mouse model of autism

  2015cited by this paper
• The oxytocin system promotes resilience to the effects of neonatal isolation on adult social attachment in female prairie voles

  2015cited by this paper
• Oxytocin Enables Maternal Behavior by Balancing Cortical Inhibition

  2015influential reference
• A sexually dimorphic hypothalamic circuit controls maternal care and oxytocin secretion

  2015cited by this paper
• An Essential Role of the Arginine Vasotocin System in Mate-Guarding Behaviors in Triadic Relationships of Medaka Fish (Oryzias latipes)

  2015cited by this paper
• RNAi knockdown of oxytocin receptor in the nucleus accumbens inhibits social attachment and parental care in monogamous female prairie voles

  2015cited by this paper
• Synaptic plasticity as a cortical coding scheme.

  2015cited by this paper
• Oxytocin modulates female sociosexual behavior through a specific class of prefrontal cortical interneurons.

  2014cited by this paper
• Role of the vasopressin 1b receptor in rodent aggressive behavior and synaptic plasticity in hippocampal area CA2

  2014cited by this paper
• Neural control of maternal and paternal behaviors

  2014cited by this paper
• The biology of mammalian parenting and its effect on offspring social development

  2014cited by this paper
• Oxytocin mediates early experience–dependent cross-modal plasticity in the sensory cortices

  2014cited by this paper
• The hippocampal CA2 region is essential for social memory

  2014cited by this paper
• Galanin neurons in the medial preoptic area govern parental behavior

  2014cited by this paper
• Oxytocin activation of neurons in ventral tegmental area and interfascicular nucleus of mouse midbrain.

  2014influential reference
• Physiological Regulation of Magnocellular Neurosecretory Cell Activity: Integration of Intrinsic, Local and Afferent Mechanisms

  2013cited by this paper
• Maternal aggression in rodents: brain oxytocin and vasopressin mediate pup defence

  2013cited by this paper
• Oxytocin enhancement of CA1 spike transmission by modulation of fast-spiking interneurons

  2013cited by this paper
• Social reward requires coordinated activity of accumbens oxytocin and 5HT

  2013cited by this paper
• Editorial comment: oxytocin, vasopressin and social behavior.

  2012cited by this paper
• Evoked axonal oxytocin release in the central amygdala attenuates fear response.

  2012influential reference
• Increasing oxytocin receptor expression in the nucleus accumbens of pre-pubertal female prairie voles enhances alloparental responsiveness and partner preference formation as adults.

  2011cited by this paper
• Multisensory integration of natural odors and sounds in the auditory cortex.

  2011cited by this paper
• Distribution and neurochemical characterization of protein kinase C-theta and -delta in the rodent hypothalamus.

  2010cited by this paper

• Oxytocin beyond social bonding: Advancing neuromodulation, synaptic plasticity, and epigenetic precision in CNS disorders.

  2026cites this paper
• Sex-dependent involvement of lateral septum astrocytes in social fear: Role of oxytocin receptor signaling

  2026cites this paper
• Multiple neural networks from cognition to motivation of prosocial behaviour in rodents: Potential mechanism between empathy and autism spectrum disorder.

  2026cites this paper
• Neural Mechanisms of Social Homeostasis: Dynamic Range Plasticity

  2026cites this paper
• The supramammillary nucleus as a multifunctional integrative hub: cell-type diversity, co-transmission, and systems-level control of behavior.

  2026cites this paper
• Oxytocin mediates the acquisition and strategy formation of cooperation in rats

  2026cites this paper
• Bivalent ligands targeting oxytocin receptor homodimers selectively activate distinct G protein and β-arrestin pathways.

  2026cites this paper
• Hilar mossy cell oxytocin receptor signaling regulates adult hippocampal neurogenesis and context discrimination in mice

  2026cites this paper
• Dissociating neural circuits of social and prosocial reward in rat helping behavior

  2026cites this paper
• Dissociable Effects of Early and Adolescent Adversity on Emotional Contagion

  2026cites this paper
• The effects of oxytocin on social behavior and eye gaze: insights from dog-human partnership.

  2026cites this paper
• Oxytocin neurons in the anterior and posterior paraventricular nucleus have distinct behavioral functions and electrophysiological profiles.

  2026cites this paper
• Astrocytes mediate a positive feedback loop for oxytocin

  2026cites this paper
• Exposure to early life social complexity shapes vasopressin and galanin neural expression in the communal spiny mouse.

  2026cites this paper
• SNAP-47 mediates somatic oxytocin dynamics in hypothalamic neurons

  2026cites this paper
• Oxytocin, Sex Hormones and Brain Activity in Facial Expression Processing: A Sex-Based Systematic Review.

  2026cites this paper
• Transcriptomic Landscape of Microglia in Mouse Models of Social Dysfunction and Oxytocin-Mediated Recovery

  2026cites this paper
• The Neuroendocrine Role of Oxytocinergic Pathways in Obesity.

  2026cites this paper
• Quantitative Determination and Stability of Trace Levels of Oxytocin in Human and Rhesus Macaque Urine by LC–MS/MS

  2026cites this paper
• Neuropeptides in control of left-right neural circuits.

  2026cites this paper
• Western lifestyle linked to maladaptive trained immunity

  2026cites this paper
• Chronic Neuroplasticity Changes Following Neurotropic Viral Infection: Mechanisms and Implications

  2025cites this paper
• Neural Circuit Remodeling Underlying Enhanced Feeding During Pregnancy in Mice

  2025cites this paper
• Role of the Oxytocinergic System in Correcting Neurogenic Impairments Induced by Early Life Stress: an in vitro Study

  2025cites this paper
• An additional mechanism of HSD3B in regulating maternal care behavior in the wolf spiders, neuropeptides.

  2025cites this paper
• Three‐dimensional quantification of oxytocin neurons in the hypothalamic paraventricular nucleus reveals sex‐ and subregion‐specific differences in two genetic mouse models of autism

  2025cites this paper
• Reduction of oxytocin plasma levels in borderline personality disorder and normalization induced by psychotherapies

  2025cites this paper
• History, pharmacology and therapeutic mechanisms of 3,4-methylenedioxymethamphetamine (MDMA).

  2025cites this paper
• Maternal care during early development is necessary for the acquisition of a calming response to back stroking

  2025cites this paper
• Oxytocin Modulates Emotion, Learning, and Memory: Insights from Advanced fMRI Analysis Techniques.

  2025cites this paper
• MDMA in Psychiatry: From PTSD to emerging indications, safety, and future directions

  2025cites this paper
• Neural basis for parental behavioral transitions in mice.

  2025cites this paper
• Oxytocin impairs wound-healing during social isolation but not social living.

  2025cites this paper
• Neuroendocrine Regulation and Neural Circuitry of Parenthood: Integrating Neuropeptides, Brain Receptors, and Maternal Behavior

  2025influential citation
• The impact of musical intervention during fetal and infant stages on social behavior and neurodevelopment in mice

  2025cites this paper
• Development and characterisation of novel oxytocin analogues for PET imaging

  2025cites this paper
• Impaired social fear extinction in chronically stressed mice: Impact on inflammatory brain markers and the contribution of oxytocin.

  2025cites this paper
• Mediating Impact of Intranasal Oxytocin on the Interaction Between Irritability and Reactive Aggression in Youth with Severe Irritability

  2025cites this paper
• Oxytocin signaling regulates maternally directed behavior during early life.

  2025cites this paper
• NGLY1 deficiency - clinical features and therapeutic strategy.

  2025cites this paper
• From trauma to resilience: psychological and epigenetic adaptations in the third generation of holocaust survivors

  2025cites this paper
• Oxytocin neurons in the anterior and posterior paraventricular nucleus have distinct behavioral functions and electrophysiological profiles

  2025cites this paper
• Sex‐Specific Long‐Term Effects of Perinatal Limosilactobacillus reuteri on Social Cognition, Gene Expression, and Gut Microbiota

  2025cites this paper
• Oxytocin-mediated empathy internally facilitates cooperative behaviors in rats.

  2025cites this paper
• Chlorpyrifos and neuroendocrine function: Concerns for research with free-living mammal populations.

  2025cites this paper
• The Role of Oxytocin in Parental Care.

  2025cites this paper
• Reviving-like prosocial behavior in response to unconscious or dead conspecifics in rodents.

  2025cites this paper
• The long-term associations of childhood parental loss with attachment, creativity, and epigenetic regulation

  2025cites this paper
• Neural plasticity supporting parental behaviors.

  2025cites this paper
• CA2 neurons show abnormal responses to social stimuli in a rat model of Fragile X syndrome

  2025cites this paper
• Assessing genetic conservation of human sociability-linked genes in C. elegans

  2025cites this paper
• The Unusual Effectiveness of Evolution in Systems Neuroscience.

  2025cites this paper
• An innate drive to save a life.

  2025cites this paper
• Oxytocin and vasopressin enhance social pain empathy via common and distinct of neural expressions, genetic pathways, and networks.

  2025cites this paper
• Oxytocin modulates inhibitory balance in the prelimbic cortex to support social memory consolidation during REM sleep

  2025cites this paper
• Oxytocin and Dopamine Receptor Expression: Cellular Level Implications for Pair Bonding

  2025cites this paper
• The Role of Oxytocin and Sex in Analgesic Placebo-Response: Exploratory Analysis from a Sham Randomized Clinical Trial in Chronic Back-Pain Patients

  2025cites this paper
• Declines in Oxytocin Receptor Density and Social Behavior Across a Dispersal‐Like Transition in Solitary Hamsters

  2025cites this paper
• Oxytocin receptors within the caudal lateral septum regulate social approach-avoidance, long-term social discrimination, and anxiety-like behaviors in adult male and female rats.

  2025cites this paper
• Prosocial Helping Behavior: Conceptual Issues and Neural Mechanisms.

  2025cites this paper
• Prolactin Shapes Cortical Plasticity in Fathers

  2025cites this paper
• The neural mechanisms supporting the rise and fall of maternal aggression

  2025cites this paper
• The Promise of Intranasal Oxytocin in Treating Borderline Personality Disorder: A Narrative Review

  2025cites this paper
• Memory Reconstruction: A Novel Therapeutic Approach to Psychosis

  2025cites this paper
• Connection and communication between the nervous and immune systems

  2025cites this paper
• Oxytocin in the Amygdala Sustains Prosocial Behavior via State-Dependent Amygdala–Prefrontal Modulation

  2025cites this paper
• Cries into ties.

  2025cites this paper
• Oxytocin facilitates human touch-induced play behavior in rats

  2025cites this paper
• The Oxytocin Neurons in the Paraventricular Nucleus Are Essential for Chronic Sleep Deprivation‐Mediated Anxiety‐Related Behaviors

  2025cites this paper
• Oxytocin as a modulator of adaptive behavior: integrating ingestive and social mechanisms.

  2025cites this paper
• Nasal dominance potentiates intranasal oxytocin’s anxiolytic effects

  2025cites this paper
• The molecular basis of music-induced neuroplasticity in humans: a systematic review.

  2025cites this paper
• Impact of sexuality on degenerative diseases.

  2025cites this paper
• Not just for bonding: Nucleus accumbens oxytocin receptors facilitate huddling with strangers and feeding in male spiny mice.

  2025cites this paper
• The psychedelic-peptide paradox: a hormetic hypothesis

  2025cites this paper
• Social bonding between humans, animals, and robots: Dogs outperform AIBOs, their robotic replicas, as social companions

  2025cites this paper
• Oxytocin and opioid antagonists: A dual approach to improving social behavior

  2025cites this paper
• The Social Salience Network Hypothesis of Autism: Disrupted Network Activity, Oxytocin Signaling, and Implications for Social Symptoms.

  2025cites this paper
• Hypothalamic Vasopressin Neurons Enable Maternal Thermoregulatory Behaviors

  2025cites this paper
• Interspecies Relational Theory: A Framework for Compassionate Interspecies Interactions

  2025cites this paper
• Oxytocin neurons signal state-dependent transitions from rest to thermogenesis and behavioral arousal in social and non-social settings

  2025cites this paper
• Borderline personality: revisiting its classification as a neurodevelopmental disorder

  2025cites this paper
• Oxytocin Neuropeptide in the Control of Drug Dependence: A Review of Past Studies and Future Challenges

  2025cites this paper
• Mapping the cellular basis of species differences in oxytocin and dopamine receptor expression in the vole nucleus accumbens

  2025cites this paper
• Are There Connections between the Neuroendocrine and Dopamine Systems in Bipolar Disorder?

  2025cites this paper
• Multi-dimensional social relationships shape social attention in monkeys

  2025cites this paper
• Rescue-like behavior in a bystander mouse toward anesthetized conspecifics promotes arousal via a tongue-brain connection

  2025cites this paper
• Effects of Intranasal Oxytocin Across Various Depressive Disorders

  2025cites this paper
• Oxytocin enhances oligodendrocyte development and improves social deficits in autistic rats

  2025cites this paper
• Development of a Methodology for Measuring Oxytocin in Feces: Insights from a Preliminary Study in Captive Lions (Panthera leo)

  2025cites this paper
• How does oxytocin modulate human behavior?

  2025cites this paper
• Intranasal oxytocin for apathy in people with frontotemporal dementia (FOXY): a multicentre, randomised, double-blind, placebo-controlled, adaptive, crossover, phase 2a/2b superiority trial.

  2025cites this paper
• Subdiaphragmatic vagotomy reduces hypothalamic oxytocin expression and blood levels after oral MDMA administration in male rats.

  2025cites this paper
• Possible brain regions involved in parturition in mice.

  2025cites this paper
• Ovarian hormone effects on cognitive flexibility in social contexts: Evidence from resting-state and task-based fMRI.

  2025cites this paper
• Male, but not female, oxytocin receptor knockout prairie voles (Microtus ochrogaster) show impaired consolation behavior.

  2025cites this paper
• Oxytocin Signaling Bridges Social and Appetitive Functions in the Rodent Hippocampus.

  2025cites this paper
• Neuronal Properties in the Lateral Habenula and Adult–Newborn Interactions in Virgin Female and Male Mice

  2025cites this paper
• The dynamic relationship of brain‐derived neurotrophic factor and oxytocin: Introducing the concept of neurosocial plasticity

  2025cites this paper
• The Hypothalamic Medial Preoptic Area–Paraventricular Nucleus Circuit Modulates Depressive-Like Behaviors in a Mouse Model of Postpartum Depression

  2025cites this paper