Humans often rank craniofacial pain as more severe than body pain. Evidence suggests that a stimulus of the same intensity induces stronger pain in the face than the body. However, the underlying neural circuitry for the differential processing of facial versus bodily pain remains unknown. Interestingly, the lateral parabrachial nucleus (PBL), a critical node in the affective pain circuit, is activated more strongly by noxious stimulation of the face than the hindpaw. Using a novel activity-dependent technology called CANE developed in our lab, we identified and selectively labeled noxious stimuli-activated PBL neurons, and performed comprehensive anatomical input-output mapping. Surprisingly, a hitherto uncharacterized monosynaptic connection between cranial sensory neurons and the PBL-nociceptive neurons was uncovered. Optogenetic activation of this monosynaptic craniofacial-to-PBL projection induced robust escape/avoidance behaviors and stress calls, whereas optogenetic silencing specifically reduced facial nociception. The monosynaptic circuit revealed here provides a neural substrate for heightened craniofacial affective pain.

Social decisions require evaluation of costs and benefits to oneself and others. Long associated with emotion and vigilance, the amygdala has recently been implicated in both decision-making and social behavior. The amygdala signals reward and punishment, as well as facial expressions and the gaze of others. Amygdala damage impairs social interactions, and the social neuropeptide oxytocin (OT) influences human social decisions, in part, by altering amygdala function. Here we show in monkeys playing a modified dictator game, in which one individual can donate or withhold rewards from another, that basolateral amygdala (BLA) neurons signaled social preferences both across trials and across days. BLA neurons mirrored the value of rewards delivered to self and others when monkeys were free to choose but not when the computer made choices for them. We also found that focal infusion of OT unilaterally into BLA weakly but significantly increased both the frequency of prosocial decisions and attention to recipients for context-specific prosocial decisions, endorsing the hypothesis that OT regulates social behavior, in part, via amygdala neuromodulation. Our findings demonstrate both neurophysiological and neuroendocrinological connections between primate amygdala and social decisions.amygdala | social decision | value mirroring | oxytocin | hierarchical modeling H ow we treat others impacts not only their well-being but our own. Human society depends on cooperation, charity, and altruism, as well as institutions to regulate selfish biases. In humans, these behaviors involve perspective-taking, empathy, and theory of mind (1, 2), and the rudiments of these capacities appear to mediate complex social behavior in animals (3). Recent research has sketched a rough outline of the neural circuits that contribute to complex social behavior (4, 5). These comprise a set of domaingeneral brain areas, including the ventromedial prefrontal cortex and ventral striatum, that process information about reward and punishment and contribute to decision-making, and a set of specialized areas, including the temporoparietal junction and medial prefrontal cortex, that process specifically social information (4, 6). How social and nonsocial signals in these circuits are integrated to mediate decisions with respect to others remains imperfectly understood, in part, due to the indirect nature of hemodynamic signals measured in human neuroimaging experiments that constitute the bulk of this research. Recent advances in the development of neurophysiological and neuropharmacological models of social decision-making, however, permit more direct inquiry into the neural mechanisms mediating other-regarding behavior (7-11).The amygdala, especially the basolateral division (BLA), has been implicated in both decision-making and social perception, inviting the possibility that it contributes to decision-making with respect to others (12)(13)(14)(15)(16)(17). This set of nuclei is well known for contributions to emotional experience and expression, especia...

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Considerable evidence implicates the basal ganglia in interval timing, yet the underlying mechanisms remain poorly understood. Using a novel behavioral task, we demonstrate that head-fixed mice can be trained to show the key features of timing behavior within a few sessions. Single-trial analysis of licking behavior reveals stepping dynamics with variable onset times, which is responsible for the canonical Gaussian distribution of timing behavior. Moreover, the duration of licking bouts decreased as mice became sated, showing a strong motivational modulation of licking bout initiation and termination. Using optogenetics, we examined the role of the basal ganglia output in interval timing. We stimulated a pathway important for licking behavior, the GABAergic output projections from the substantia nigra pars reticulata to the deep layers of the superior colliculus. We found that stimulation of this pathway not only cancelled licking but also delayed the initiation of anticipatory licking for the next interval in a frequency-dependent manner. By combining quantitative behavioral analysis with optogenetics in the head-fixed setup, we established a new approach for studying the neural basis of interval timing.