探討自臂旁核到腹側被蓋區的神經輸入對進食之調控

Abstract

雖然研究指出旁臂核會傳遞與厭惡相關的訊息，例如內臟不適、疼痛、搔癢，與提示相關之潛在威脅，旁臂核至腹側被蓋區迴路的功能尚不清楚。本實驗室先前研究發現，促進表現麩胺酸之旁臂核至腹側被蓋區迴路，抑制了小鼠自主取食的行為。為進一步探討旁臂核至腹側被蓋區迴路之功能，我透過逆向標記投射至腹側被蓋區之旁臂核神經元，並結合神經活動之生物標記c-Fos的免疫染色，進而發現一部分投射至腹側被蓋區之旁臂核神經元，功能性地參與壓力、恐懼，而非進食、內臟不適，或焦慮。這些結果暗示旁臂核可能可以將負面情緒如壓力和恐懼，傳入腹側被蓋區。為尋找在訊息自旁臂核傳入腹側被蓋區後，接續傳遞訊息的下游媒介，我使用了順向標記與仰賴神經活動之標記方法 (標記並基因重組活化之神經元)，分別標記受旁臂核支配與活化的腹側被蓋區神經元。雖然旁臂核在構造上支配表現多巴胺與非多巴胺的神經元，我發現旁臂核在功能上主要活化非多巴胺神經元。再者，這些神經元投射至數個下游腦區，其中包含外側下視丘柄部與外側疆核。整體來說，這些結果顯示旁臂核可能透過腹側被蓋區，來傳遞負面情緒而調節進食行為。

Although the parabrachial nucleus (PBN) has been shown to relay signals associated with aversion, such as visceral malaise, pain, itch, and cues associated with potential threats, the function of its efferent projection to the ventral tegmental area (VTA) remains elusive. Previous studies in the lab have discovered that enhancing the PBN-to-VTA excitatory glutamatergic inputs dampens food self-administration behaviors. To further investigate the function roles of the PBN-to-VTA input, I first employed retrograde targeting approach to selectively target VTA-projecting PBN neurons. By combining activity-dependent c-Fos staining with different behavioral paradigms, I found that subpopulations of VTA-projecting PBN neurons were functionally involved in stress and fear, but not feeding, malaise or anxiety. These results suggest that the PBN-to-VTA inputs may relay aversive emotions such as stress and fear. To specify the downstream mediator of the PBN-to-VTA inputs, I employed the anterograde targeting and activity-dependent targeting (Targeted Recombination in Active Populations, TRAP) approaches to selectively target VTA neurons innervated and activated by the PBN input, respectively. Despite that PBN input anatomically innervated both the VTA DA and non-DA neurons, I found that the PBN input functionally recruited mostly non-dopaminergic cells. Moreover, these neurons sent projections to several downstream brain regions, including peduncular part of lateral hypothalamus (PLH) and lateral habenula (LHb). Considered together, these results suggest the PBN may relay negative emotion through the VTA to override food seeking behaviors.