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.

Predictors of Prolonged Mechanical Ventilation Among Patients with Aneurysmal Subarachnoid Hemorrhage After Microsurgical Clipping.

INTRODUCTION: Aneurysmal subarachnoid hemorrhage (aSAH) is a fatal event with high mortality and morbidity rates. Survivors may require prolonged intubation with mechanical ventilation (MV). However, the risk factors for prolonged intubation in these patients remain unclear. The aim of this study was to determine the predictors of prolonged MV in aSAH patients who underwent surgical clipping. METHODS: In total, 108 adult patients with a primary diagnosis of aSAH who were on MV > 48 h and survived > 14 days after surgery were included. Clinicodemographic and radiological characteristics, laboratory tests on admission, and initial Glasgow Coma Scale (GCS) and its components were analyzed. RESULTS: The average age of the patients included in the analysis was 59.1 ± 12.5 years. Overall, 32 patients (29.6%) had prolonged MV. The group with prolonged MV showed a higher prevalence of diabetes mellitus and hypertension, lower initial GCS and its components, higher World Federation of Neurosurgeons (WFNS) and Hunt and Hess grades, and higher initial white cell counts. The independent factors associated with prolonged MV were a history of diabetes mellitus (odds ratio [OR] 5.799, 95% confidence interval [CI] 1.109-30.334; P = 0.037) and Hunt and Hess grade 3-5 (OR 7.217, 95% CI 1.090-47.770; P = 0.040). CONCLUSION: A history of diabetes mellitus and Hunt and Hess grade 3-5 independently predict prolonged MV after microsurgical clipping in patients with aSAH. Thus, knowledge of potential predictors for prolonged MV is essential to improve the early initiation of adequate treatment in the early stages of treatment and provide useful information for communication between caregivers and families.