| Popis: |
To survive and thrive in a complex social group, it is essential to not only know who to approach but more importantly who to avoid. After a single defeat, mice learn to stay away from the winning aggressor for weeks. Here, we identify oxytocin neurons in the retrochiasmatic supraoptic nucleus (SOROXT) and oxytocin receptor 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, aVMHvlOXTRcells drastically increase their responses to aggressor cues. This response change is functionally important as optogenetic activation of aVMHvlOXTRcells 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. aVMHvlOXTRreceives its private source of oxytocin from SOROXTcells, which are highly activated by the noxious somatosensory inputs associated with defeat. Oxytocin released from SOROXTdepolarizes aVMHvlOXTRcells and facilitates their synaptic potentiation, and hence, increases aVMHvlOXTRcell responses to aggressor cues. Ablating SOROXTcells 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-aVMHvlOXTRcircuit in defeat-induced social learning and highlights the importance of brain oxytocin system in social plasticity. |
