建構果蠅腦內影響動機的神經網路圖譜

Mapping Motivation Circuits in the Drosophila Brain

邱美慈

指導教授 ： 江安世

國立清華大學/生命科學院/生物科技研究所/碩士(2013年)

摘要

神經胜肽是一種神經元的信號分子，他們能調節廣泛的生理及行為。果蠅神經胜肽F（NPF）是一種與哺乳類的神經胜肽Y (NPY) 同源的胜肽，並且能夠調控多種大腦的功能，尤其是飢餓引發的動機反應;而其可以加速長期記憶的形成。為了能深入了解如何透過NPF信號的傳遞來調節動機與記憶行為，最主要的步驟是要先了解NPF的神經元網路分布以及了解神經之間的訊號是如何流動。在這個研究裡，我們分析NPF與其受器NPFR1的神經網路。我們發現一對位於前外側的神經(DAL2)神經元同時表現了NPF 受器以及NMDA受器，且與長期記憶相關的DAL神經元在dorso-frontal protocerebrum（SDFP）的區域有結構性連結。因此我們推測DAL2神經元釋放出的NPF的信號可被在DAL上的NPFR1接收而調控果蠅的長期記憶，另外，神經極性分析結果顯示，NPF的訊號可能被DAL2神經元接收，透過這樣的自體反回饋機制，來增加DAL2本身以及其下游DAL神經元的活性。在果蠅成蟲腦裡，我們也發現NPFR1會表現在部分多巴胺神經元上，而NPF訊號可能藉由多巴胺神經上的NPFR1，將NPF訊號導入多巴胺神經系統，而調節食慾或厭惡的記憶行為。且NPF神經元DAL2也與多巴胺神經元在SDFP也有結構性的連結。這些結果顯示有三條NPF/NPFR1資訊流通的路徑，分別為DAL2 (NPF) 至多巴胺神經元、DAL2 (NPF)至DAL (NPFR1)神經元和DAL2 (NPF) 傳至DAL2 (NPFR1)神經元，這三條路徑都主要在SDFP區域有連結，來調控多種相關的行為反應。

關鍵字

果蠅 ； 動機 ； 神經胜肽F

並列摘要

Neuropeptides are a group of neuronal signalling molecules that modulate a wide range of physiological processes and behaviors. The Drosophila neuropeptide F (NPF), a homolog to human NPY, is involved in a wide range of brain functions, especially hunger-induced motivational response which can facilitate the Long-term memory (LTM) formation. To understand how NPF signals are transmitted and regulate motivational and memory behaviors, it is critical to know the circuitry wiring and connectome of NPF neurons. Here, we analysed NPF positive neurons and their receptor NPFR1 neurons. A pair of NPF-positive dorsal-anterior-lateral2 (DAL2) neurons was demonstrated also NPFR1 and NMDAR positive have structured connections with LTM neuron-DAL in superior dorsofrontal protocerebrum (SDFP) region. We postulated that the DAL2 releases NPF signals received by NPFR1 in the DAL neuron to regulate long-term memory. Polarity analysis showed the DAL2 neurons could receive NPF signal through an autocrine feedback mechanism to increase the activity of themselves and their downstream DAL neurons. In the adult brain, subsets of dopaminergic neurons expressed NPFR1 that might conduct the NPF signals into the dopaminergic (DA) system which involve in appetitive and aversive memory behaviour. And the NPF-positive DAL2 neuron also have structured connections with DA neurons in the SDFP region. These findings suggested three information flowing pathways from NPF to NPFR1, (i) DAL2 (NPF) --> DA neurons, (ii) DAL2 (NPF) --> DAL (NPFR1), and (iii) DAL2 (NPF) --> DAL2 (NPFR1), all connection major in the SDFP region to modulate relative behaviours.

參考文獻

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