Social rank modulates empathic pain via Galntl6

Considerable individual variations in empathic abilities have been observed, but the contributing factors and underlying neural mechanisms remain poorly understood. Dominance hierarchy is a fundamental phenomenon in grouped animals and human beings, which has a profound impact on mental health and behaviors. Here, we show that social rank modulates empathic pain responses, with subordinate mice displaying significantly stronger empathic pain than dominant counterparts. Our findings reveal that the glutamatergic projection from the anterior cingulate cortex (ACC) to the nucleus accumbens core (NAcC) is critical for the development of empathic pain in subordinate mice. Selective activation of the ACC-NAcC pathway enhances empathic pain intensity in dominant mice, whereas inhibition of the pathway attenuates such responses in subordinate mice. Through synaptic molecular screening, we identified Galntl6 as a key regulator of enhanced synaptic glutamate transmission from ACC to D1-type medium spiny neurons (D1 MSNs) in the NAcC. Collectively, these findings provide a framework for understanding the neural basis of the impact of social status on empathic pain.