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Anterior Cingulate Inputs to Nucleus Accumbens, Pain and Analgesia
Science 08 Jan 2021, Vol. 371, Issue 6525, pp. 153-159 Anterior cingulate inputs to nucleus accumbens control the social transfer of pain and analgesia Smith, et.al. Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA [paraphrase] Empathy is an essential component of social communication that involves experiencing others’ sensory and emotional states. We observed 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 demonstrated that the anterior cingulate cortex (ACC) and its projections to the nucleus accumbens (NAc) were selectively involved in the social transfer of both pain and analgesia. By contrast, the ACC→NAc circuit was not necessary for the social transfer of fear, which instead depended on ACC projections to the basolateral amygdala. These findings reveal that the ACC, a brain area strongly implicated in human empathic responses, mediates distinct forms of empathy in mice by influencing different downstream targets. The anterior cingulate cortex (ACC) is a principal node in the neural circuitry thought to mediate empathy. In both humans and rodents, the ACC is particularly critical for affective and motivational responses to direct and observed pain as well as the social transfer of pain. The ACC is thought to communicate with a broad range of brain regions that regulate emotional and motivational states, including the thalamus, insula, amygdala, and nucleus accumbens (NAc). However, the roles of these specific ACC circuit elements in empathy-related behaviors are unknown. · Rapid transfer of pain behavior to bystander mice · Activation of an ACC-to-NAc core circuit by the social transfer of pain · ACC-to-NAc projections bidirectionally control social transfer of pain · Distinct ACC projections control the social transfer of pain and fear · ACC-to-NAc projections regulate the social transfer of analgesia These results suggest that the ACC, which has been proposed to be a key brain area for mediating the emotional aspects of pain as well as encoding information about the affective state of others, generates a specific and appropriate empathic behavioral response by accessing distinct downstream targets. The specificity of the neural circuit and behavioral response generated during socially transferred pain and fear may be, at least in part, due to the sensory modalities required for these two forms of social transfer. The social transfer of pain does not require visual or auditory stimuli but can be generated by exposure to used bedding from mice experiencing pain, suggesting that olfactory cues are sufficient for this form of social transfer. By contrast, the social transfer of fear requires visual and/or auditory cues. Further elucidation of the mechanisms by which this specificity in empathic neural and behavioral responses occurs will be important for developing interventions that promote social context–appropriate empathic responses. Furthermore, a better understanding of the neural circuits mediating specific empathic responses will greatly facilitate the development of therapies that target pathological forms of empathy, or its absence, in a variety of neuropsychiatric disorders. Historically, empathy, as defined by the ability to experience and share the emotions of others, was often considered to be a high level, affective-cognitive process experienced almost exclusively by humans. However, most investigators now accept that empathy can be deconstructed into specifiable, evolutionarily conserved components, many of which can be studied in rodents to elucidate their underling neural mechanisms. Our results provide additional evidence that mice can rapidly and reliably adopt the sensory-affective state of a social partner, regardless of the valence of the information (pain, fear, or pain relief). Although it is conceivable that the behavioral responses of our BY mice reflect “imitative” or “mimicry” behavior rather than “empathy,” several findings suggest that at least for the social transfer of pain and analgesia, the BY mice manifest changes in their behavior because they are experiencing an altered sensory-affective state. Importantly, the BY mice were tested using several different behavioral assays and did not always have direct visual access to their social partners during testing. In addition, control mice spent more time interacting with a BY mouse that had recently been exposed to a CFA mouse than with another control mouse, indicating that the BY mouse is in an altered affective state that is sufficient to attract control mice. Finally, as mentioned above, the social transfer of pain can be generated by bedding (9), which provides no opportunity for imitative or mimicry-like behavior. [end of paraphrase] |
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Anterior Cingulate Inputs to Nucleus Accumbens, Pain and Analgesia
Science 08 Jan 2021, Vol. 371, Issue 6525, pp. 153-159 Anterior cingulate inputs to nucleus accumbens control the social transfer of pain and analgesia Smith, et.al. Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA [paraphrase] Empathy is an essential component of social communication that involves experiencing others’ sensory and emotional states. We observed 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 demonstrated that the anterior cingulate cortex (ACC) and its projections to the nucleus accumbens (NAc) were selectively involved in the social transfer of both pain and analgesia. By contrast, the ACC→NAc circuit was not necessary for the social transfer of fear, which instead depended on ACC projections to the basolateral amygdala. These findings reveal that the ACC, a brain area strongly implicated in human empathic responses, mediates distinct forms of empathy in mice by influencing different downstream targets. The anterior cingulate cortex (ACC) is a principal node in the neural circuitry thought to mediate empathy. In both humans and rodents, the ACC is particularly critical for affective and motivational responses to direct and observed pain as well as the social transfer of pain. The ACC is thought to communicate with a broad range of brain regions that regulate emotional and motivational states, including the thalamus, insula, amygdala, and nucleus accumbens (NAc). However, the roles of these specific ACC circuit elements in empathy-related behaviors are unknown. · Rapid transfer of pain behavior to bystander mice · Activation of an ACC-to-NAc core circuit by the social transfer of pain · ACC-to-NAc projections bidirectionally control social transfer of pain · Distinct ACC projections control the social transfer of pain and fear · ACC-to-NAc projections regulate the social transfer of analgesia These results suggest that the ACC, which has been proposed to be a key brain area for mediating the emotional aspects of pain as well as encoding information about the affective state of others, generates a specific and appropriate empathic behavioral response by accessing distinct downstream targets. The specificity of the neural circuit and behavioral response generated during socially transferred pain and fear may be, at least in part, due to the sensory modalities required for these two forms of social transfer. The social transfer of pain does not require visual or auditory stimuli but can be generated by exposure to used bedding from mice experiencing pain, suggesting that olfactory cues are sufficient for this form of social transfer. By contrast, the social transfer of fear requires visual and/or auditory cues. Further elucidation of the mechanisms by which this specificity in empathic neural and behavioral responses occurs will be important for developing interventions that promote social context–appropriate empathic responses. Furthermore, a better understanding of the neural circuits mediating specific empathic responses will greatly facilitate the development of therapies that target pathological forms of empathy, or its absence, in a variety of neuropsychiatric disorders. Historically, empathy, as defined by the ability to experience and share the emotions of others, was often considered to be a high level, affective-cognitive process experienced almost exclusively by humans. However, most investigators now accept that empathy can be deconstructed into specifiable, evolutionarily conserved components, many of which can be studied in rodents to elucidate their underling neural mechanisms. Our results provide additional evidence that mice can rapidly and reliably adopt the sensory-affective state of a social partner, regardless of the valence of the information (pain, fear, or pain relief). Although it is conceivable that the behavioral responses of our BY mice reflect “imitative” or “mimicry” behavior rather than “empathy,” several findings suggest that at least for the social transfer of pain and analgesia, the BY mice manifest changes in their behavior because they are experiencing an altered sensory-affective state. Importantly, the BY mice were tested using several different behavioral assays and did not always have direct visual access to their social partners during testing. In addition, control mice spent more time interacting with a BY mouse that had recently been exposed to a CFA mouse than with another control mouse, indicating that the BY mouse is in an altered affective state that is sufficient to attract control mice. Finally, as mentioned above, the social transfer of pain can be generated by bedding, which provides no opportunity for imitative or mimicry-like behavior. [end of paraphrase] |