defeat

Decoding stress vulnerability

Although stress can be considered as an ongoing process that helps an organism to cope with present and future challenges, when it is too intense or uncontrollable, it can lead to adverse consequences for physical and mental health. Social stress specifically, is a highly prevalent traumatic experience, present in multiple contexts, such as war, bullying and interpersonal violence, and it has been linked with increased risk for major depression and anxiety disorders. Nevertheless, not all individuals exposed to strong stressful events develop psychopathology, with the mechanisms of resilience and vulnerability being still under investigation. During this talk, I will identify key gaps in our knowledge about stress vulnerability and I will present our recent data from our contextual fear learning protocol based on social defeat stress in mice.

Mapping the neural dynamics of dominance and defeat

Social experiences can have lasting changes on behavior and affective state. In particular, repeated wins and losses during fighting can facilitate and suppress future aggressive behavior, leading to persistent high aggression or low aggression states. We use a combination of techniques for multi-region neural recording, perturbation, behavioral analysis, and modeling to understand how nodes in the brain’s subcortical “social decision-making network” encode and transform aggressive motivation into action, and how these circuits change following social experience.

Private oxytocin supply and its receptors in the hypothalamus for social avoidance learning

Many animals live in complex social groups. To survive, it is essential to know who to avoid and who to interact. Although naïve mice are naturally attracted to any adult conspecifics, a single defeat experience could elicit social avoidance towards the aggressor for days. The neural mechanisms underlying the behavior switch from social approach to social avoidance remains incompletely understood. Here, we identify oxytocin neurons in the retrochiasmatic supraoptic nucleus (SOROXT) and oxytocin receptor (OXTR) expressing cells in the anterior subdivision of ventromedial hypothalamus, ventrolateral part (aVMHvlOXTR) as a key circuit motif for defeat-induced social avoidance learning. After defeat, aVMHvlOXTR cells drastically increase their responses to aggressor cues. This response change is functionally important as optogenetic activation of aVMHvlOXTR cells elicits time-locked social avoidance towards a benign social target whereas inactivating the cells suppresses defeat-induced social avoidance. Furthermore, OXTR in the aVMHvl is itself essential for the behavior change. Knocking out OXTR in the aVMHvl or antagonizing the receptor during defeat, but not during post-defeat social interaction, impairs defeat-induced social avoidance. aVMHvlOXTR receives its private supply of oxytocin from SOROXT cells. SOROXT is highly activated by the noxious somatosensory inputs associated with defeat. Oxytocin released from SOROXT depolarizes aVMHvlOXTR cells and facilitates their synaptic potentiation, and hence, increases aVMHvlOXTR cell responses to aggressor cues. Ablating SOROXT cells impairs defeat-induced social avoidance learning whereas activating the cells promotes social avoidance after a subthreshold defeat experience. Altogether, our study reveals an essential role of SOROXT-aVMHvlOXTR circuit in defeat-induced social learning and highlights the importance of hypothalamic oxytocin system in social ranking and its plasticity.

“Empowering the immune system helps defeat dementia: The key role of monocyte-derived macrophages”

Mapping the neural dynamics of social dominance and defeat

Mapping the neural dynamics of social dominance and defeat

Effects of chronic stress on hippocampal microglia and neurogenesis of mice under social defeat stress

Role of the medial amygdala glutamatergic and GABAergic neurons during social defeat

FENS Forum 2024

Anxiety levels after vicarious social defeat stress are associated with vulnerability and resilience to cocaine-induced conditioned place preference in female mice

Automatically annotated motion tracking identifies a distinct social behavioral profile following chronic social defeat stress

Brain stress and noradrenergic system mediate the mechanisms underlying relapse caused by exposure to Social Defeat in the nucleus accumbens in morphine dependent mice

Does physical exercise offer resilience in a social defeat stress mouse model?

H3K4me3 epigenetic signatures in social defeat stress of varying duration

Meta-analysis of prefrontal cortex RNA-seq data after social defeat stress of varying duration

Mir-34 family is involved in Chronic Social Defeat-induced vulnerability to mood disorders and cardiac mitochondrial dysfunctions

Newly Formed Synapses Between VTA Projections and ACC Pyramidal Neurons in Response to Chronic Social Defeat Stress Differentiate Stress Susceptible From Stress Resilient Mice

Role of immediate early genes in neural plasticity during social defeat

Social defeat during adolescence increases the susceptibility to an immune challenge later in life

Social defeat stress induces microglial alterations and impaired cell survival in the hypothalamus according to behavioral phenotype

The analyses of neural basis for individual differences in behavioral outcomes caused by long-term social defeat stress in mice

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Brain-wide scale neuronal activation of behavioral outcomes following learned helplessness and acute social defeat stress in mice

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Female microglia and neurogenesis respond differently to social defeat stress compared to males

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Intermittent access to a high-fat diet blocks the increase in ethanol consumption and the neuroinflammatory response induced by social defeat in adult male mice

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Ketogenic diet buffers brain gene expression and ethanol consumption induced by vicarious social defeat exposure in female mice

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TPH2 knockout rats cannot accept social defeat in resident-intruder test

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Raphe nucleus function in aversive valence processing between adaptive learning and social defeat in zebrafish

FENS Forum 2024