Social touch-like tactile stimulation activates a tachykinin 1-oxytocin pathway to promote social interactions

• Published in: Neuron (Cambridge, Mass.) Mass.), 2022-03, Vol.110 (6), p.1051-1067.e7
• Main Authors: Yu, Hang, Miao, Wanying, Ji, En, Huang, Shajin, Jin, Sen, Zhu, Xutao, Liu, Ming-Zhe, Sun, Yan-Gang, Xu, Fuqiang, Yu, Xiang
• Format: Article
• Language: English
• Subjects: Animals; Mice; neuronal firing; oxytocin; Oxytocin - metabolism; PAG; PVH; Social Interaction; social touch; substance P; tachykinin 1; Tachykinins; Touch; Touch Perception
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2021.12.022

It is well known that affective and pleasant touch promotes individual well-being and facilitates affiliative social communication, although the neural circuit that mediates this process is largely unknown. Here, we show that social-touch-like tactile stimulation (ST) enhances firing of oxytocin neurons in the mouse paraventricular hypothalamus (PVH) and promotes social interactions and positively reinforcing place preference. These results link pleasant somatosensory stimulation to increased social interactions and positive affective valence. We further show that tachykinin 1 (Tac1+) neurons in the lateral and ventrolateral periaqueductal gray (l/vlPAG) send monosynaptic excitatory projections to PVH oxytocin neurons. Functionally, activation of PVH-projecting Tac1+ neurons increases firing of oxytocin neurons, promotes social interactions, and increases preference for the social touch context, whereas reducing activity of Tac1+ neurons abolishes ST-induced oxytocin neuronal firing. Together, these results identify a dipeptidergic pathway from l/vlPAG Tac1+ neurons to PVH oxytocin neurons, through which pleasant sensory experience promotes social behavior. [Display omitted] •Social touch enhances oxytocin neuronal firing, social interactions, and CPP•l/vlPAG Tac1+ neurons send monosynaptic excitatory inputs to PVH oxytocin neurons•Activation of PVH-projecting l/vlPAG Tac1+ neurons promotes oxytocin neuronal firing•Activation of PVH-projecting l/vlPAG Tac1+ neurons promotes social interactions Yu et al. identified a dipeptidergic circuit through which pleasant touch experience promotes social interactions and preference for the touch context. Tachykinin neurons in the periaqueductal gray function as a critical sensory relay node for enhancing oxytocin neuronal firing in the paraventricular nuclei and for promoting social interactions.