探討臂旁核相異神經輸出之迴路特性與行為功能

Abstract

臂旁核（parabrachial nucleus, PBN）整合來自外界的厭惡性刺激與生物內在的狀態，進而透過不同的下游腦區來驅動相應的行為反應。過往研究指出，PBN投射至腹側被蓋區（ventral tegmental area, VTA）以及前側丘腦室旁核（anterior part of the paraventricular nucleus of the thalamus, aPVT），這兩個區域皆與動機性行為的調控有關。然而，PBN如何透過與此兩腦區的神經連結來調控行為仍是未知。在本研究中，我運用Targeted Recombination in Active Populations（TRAP）技術發現，PBN神經輸入所活化的VTA神經元主要為非多巴胺性神經元，且對這些標定到的特定VTA細胞進行光遺傳刺激會引發厭惡反應，並足以中斷小鼠正在進行的尋食行為。相較之下，活化PBN投射至aPVT的神經連結則抑制輕度的進食動機，但不會引發厭惡感而是提升小鼠的警覺程度。研究結果顯示出PBN透過兩下游連結之相異神經機制來調控小鼠進食行為。此外，我也發現腹側海馬迴（ventral hippocampus, vHip）為aPVT的另一上游腦區，並揭示了PBN與vHip投射至aPVT的兩神經迴路在解剖連結與行為功能上的差異。

The parabrachial nucleus (PBN) integrates aversive stimuli and internal states to subsequently guide coping responses via different downstream regions. Previous studies have showed that the PBN projects to both the ventral tegmental area (VTA) and the anterior part of the paraventricular nucleus of the thalamus (aPVT), two regions implicated in the modulation of motivational behaviors. However, the functional roles of these two pathways remain elusive. In the present study, using the Targeted Recombination in Active Populations (TRAP) approach, I deciphered that PBN afferents activation recruited non-dopaminergic neurons in the VTA, and photoactivation of the TRAPed VTA cells induced aversion and was sufficient to disengage ongoing food-seeking behavior. In contrast, photoactivation of PBN-to-aPVT connection disrupted mild food intake motivation, and enhanced arousal without inducing aversion. Additionally, I identified the ventral hippocampus (vHip) as an upstream input to the aPVT, and revealed distinct anatomical connections and behavioral functions between the PBN-to-aPVT and vHip-to-aPVT pathways.