Negative Emotions Recruit the Parabrachial Nucleus Efferent to the VTA to Disengage Instrumental Food Seeking.

The parabrachial nucleus (PBN) interfaces between taste and feeding systems and is also an important hub for relaying distress information and threats. Despite that the PBN sends projections to the ventral tegmental area (VTA), a heterogeneous brain region that regulates motivational behaviors, the function of the PBN-to-VTA connection remains elusive. Here, by using male mice in several behavioral paradigms, we discover that VTA-projecting PBN neurons are significantly engaged in contextual fear, restraint or mild stress but not palatable feeding, visceral malaise, or thermal pain. These results suggest that the PBN-to-VTA input may relay negative emotions under threat. Consistent with this notion, optogenetic activation of PBN-to-VTA glutamatergic input results in aversion, which is sufficient to override palatable feeding. Moreover, in a palatable food-reinforced operant task, we demonstrate that transient optogenetic activation of PBN-to-VTA input during food reward retrieval disengages instrumental food-seeking behaviors but spares learned action-outcome association. By using an activity-dependent targeting approach, we show that VTA DA neurons are disengaged by the PBN afferent activation, implicating that VTA non-DA neurons may mediate PBN afferent regulation. We further show that optogenetic activation of VTA neurons functionally recruited by the PBN input results in aversion, dampens palatable feeding, and disengages palatable food self-administration behavior. Finally, we demonstrate that transient activation of VTA glutamatergic, but not GABAergic, neurons recapitulates the negative regulation of the PBN input on food self-administration behavior. Together, we reveal that the PBN-to-VTA input conveys negative affect, likely through VTA glutamatergic neurons, to disengage instrumental food-seeking behaviors.SIGNIFICANCE STATEMENT The PBN receives multiple inputs and thus is well positioned to route information of various modalities to engage different downstream circuits to attend or respond accordingly. We demonstrate that the PBN-to-VTA input conveys negative affect and then triggers adaptive prioritized responses to address pertinent needs by withholding ongoing behaviors, such as palatable food seeking or intake shown in the present study. It has evolutionary significance because preparing to cope with stressful situations or threats takes priority over food seeking to promote survival. Knowing how appropriate adaptive responses are generated will provide new insights into circuitry mechanisms of various coping behaviors to changing environmental stimuli.

Predictive processing, cognitive control, and tonality stability of music: An fMRI study of chromatic harmony.

The present study aimed at identifying the brain regions which preferentially responded to music with medium degrees of key stability. There were three types of auditory stimuli. Diatonic music based strictly on major and minor scales has the highest key stability, whereas atonal music has the lowest key stability. Between these two extremes, chromatic music is characterized by sophisticated uses of out-of-key notes, which challenge the internal model of musical pitch and lead to higher precision-weighted prediction error compared to diatonic and atonal music. The brain activity of 29 adults with excellent relative pitch was measured with functional magnetic resonance imaging while they listened to diatonic music, chromatic music, and atonal random note sequences. Several frontoparietal regions showed significantly greater response to chromatic music than to diatonic music and atonal sequences, including the pre-supplementary motor area (extending into the dorsal anterior cingulate cortex), dorsolateral prefrontal cortex, rostrolateral prefrontal cortex, intraparietal sulcus, and precuneus. We suggest that these frontoparietal regions may support working memory processes, hierarchical sequencing, and conflict resolution of remotely related harmonic elements during the predictive processing of chromatic music. This finding suggested a possible correlation between precision-weighted prediction error and the frontoparietal regions implicated in cognitive control.