Social transmission of pain and relief
In mice, pain and fear can be transmitted through brief social contact from one animal to a bystander. Neurons in a region of the brain, called the anterior cingular cortex in the bystander, mediate these transfers. However, the specific leading cinglate projections involved in such empathy-related behaviors are unknown. Smith et al. found that projections from the anterior cingular cortex to the nucleus accumbens are necessary for the social transmission of pain in mice (see the Perspective by Klein and Gogolla). However, fear is mediated by projections from the anterior cingular cortex to the basolateral amygdala. Interestingly, analgesic analgesia can also be socially transmitted.
Science, this issue p. 153; see also p. 122
Structured summary
INTRODUCTION
Empathy, the acceptance of another’s sensory and emotional state, plays a critical role in social interactions. Although empathy has historically often been viewed as an affective-cognitive process experienced only by humans, it is now appreciated that many species, including rodents, display evolutionarily conserved behavioral predictors of empathy, such as observational anxiety. It is therefore possible to begin to define the neural mechanisms that mediate behavioral manifestations of empathy in species that are optimal for the application of modern neuroscience equipment.
RATIONALE
In both humans and rodents, the anterior cingular cortex (ACC) appears to contain information about the affective state of others. However, little is known about the downstream targets of the ACC that contribute to empathy-related behaviors. To address this topic, we have optimized a protocol for the social transmission of pain behavior in mice and compared the ACC-dependent neural circuits responsible for this behavior with the ACC neural circuits required for the social transmission of two related behavioral states: analgesia and fear. This behavior shows an important component of empathy, the acceptance of another’s sensory and affective state.
RESULTS
A 1-hour social interaction between a bystander mouse and a kagat experiencing inflammatory pain resulted in mechanical hyperalgesia in the bystander mouse, which lasted 4 hours but not 24 hours. This social transmission of pain was also evident after thermal testing and led to affective changes detected by a specialist. The social interaction led to activation of neurons in the ACC and several downstream targets, including the nucleus accumbens (NAc), which were revealed by monosynaptic rabies virus detected to be directly linked to the ACC. Two-way manipulation of activity in ACC-to-NAc inputs affects the acquisition of socially-transmitted pain, but not the expression of the mechanical sensitivity used to determine pain thresholds. A behavioral protocol revealed the rapid social transmission of analgesia, which also required activity in ACC-to-NAc inputs. In contrast, ACC-to-NAc input activity was not required for the social transmission of fear, which rather required activity in ACC projections to the basolateral amygdala (BLA).
CLOSURE
We found that mice quickly assume the sensory affective state of a social partner, regardless of the value of the information (i.e., pain, fear, or pain relief). We find that the ACC generates specific and appropriate empathic behavioral responses through different downstream targets. Specifically, ACC-to-NAc input activity is required for the social transmission of pain and analgesic, but not the social transmission of fear, which rather requires ACC-to-BLA input activity. To elucidate circuit-specific mechanisms that mediate different forms of empathy in experimentally accessible animal models, it is necessary to generate hypotheses that can be evaluated in human subjects using non-invasive assessments. More sophisticated understanding of evolutionarily conserved brain mechanisms of empathy will also accelerate the development of new therapies for the empathy-related deficits associated with a wide range of neuropsychiatric disorders.
Complete Freund’s adjuvant (CFA) -induced pain is transmitted to bystanders to bystanders after a 1 hour social interaction. Bystanders also display pain relief after interacting with cage mates who experience pain and morphine analgesia. The social transfer of pain and analgesia both require ACC-to-NAc projections, while the social transfer of fear requires ACC projections to the BLA. Data represent mean ± SEM; dotted line indicates the average base threshold for all groups; **P <0.01 and ****P <0.0001.
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Complete Freund’s adjuvant (CFA) -induced pain is transmitted to bystanders to bystanders after a 1 hour social interaction. Bystanders also display pain relief after interacting with cage mates who experience pain and morphine analgesia. The social transfer of pain and analgesia both require ACC-to-NAc projections, while the social transfer of fear requires ACC projections to the BLA. Data represent mean ± SEM; dotted line indicates the average baseline threshold for all groups; **P <0.01 and ****P <0.0001.
Abstract
Empathy is an essential component of social communication that involves the experience of others’ sensory and emotional states. We noted that a brief social interaction with a mouse experiencing pain or morphine analgesia resulted in the transfer of these experiences to its social partner. Optogenetic manipulations have shown that the anterior cingulate cortex (ACC) and its projections to the nucleus accumbens (NAc) were selectively involved in the social transmission of pain and analgesia. In contrast, the ACC → NAc circuit was not required for the social transmission of fear, which was rather dependent on ACC projections to the basolateral amygdala. These findings reveal that the ACC, a brain region strongly involved in human empathic responses, mediates different forms of empathy in mice by influencing different downstream targets.