Investigating the transcriptional and functional stress responses in different neuron subtypes after knockdown of mitochondrial complex I subunit ND-7

我们假设线粒体复合物I抑制（通过敲低亚基ND-75）将导致不同的神经元亚型不同的转录和功能应激反应。为了在接下来的几个月里验证这个假设，我计划：1。分析ND-75 KD在单个神经元亚型多巴胺能和多巴胺能神经元中的行为效应。攀爬和癫痫发作试验CAF 1摄食试验ANY-迷宫开放视野试验热板试验ATF 4表达分析-成人脑解剖、染色和共聚焦显微镜2.分析单个神经元中ND-75 KD引起的转录反应。- 我们将从具有泛神经元ND-75 KD和ND-75 KD以及ATF 4 KD的果蝇进行单核RNA-seq（snRNA-seq）。测试靶向线粒体应激信号传导是否改变多巴胺能和多巴胺能神经元功能。

We hypothesise that mitochondrial complex I inhibition (via knock down of subunit ND-75) will lead to distinct transcriptional and functional stress responses in different neuronal subtypes. To test this hypothesis in the next upcoming months I plan to:1. Analyze the behavioural effects of ND-75 KD in a single neuronal subtype, dopaminergic and serotonergic neurons.Climbing and seizure assaysCAFÉ feeding assayANY-Maze open field assayHot plate assayAnalysis of ATF4 expression- adult brain dissections, staining and confocal microscopy 2. Analyze the transcriptional response caused by ND-75 KD in single neurons. -We will perform single nuclear RNA-seq (snRNA-seq) from flies with pan-neuronal ND-75 KD and ND-75 KD together with ATF4 KD.3. Test whether targeting mitochondrial stress signalling modifies dopaminergic and serotonergic neuron function.