Sun Jun, Xu An Qi, Giraud Julia, Poppinga Haiko, Riemensperger Thomas, Fiala André, Birman Serge
Genes Circuits Rhythms and Neuropathology, Brain Plasticity Unit, Centre National de la Recherche Scientifique, PSL Research University, ESPCI Paris, Paris, France.
Department of Molecular Neurobiology of Behavior, Johann-Friedrich-Blumenbach-Institute for Zoology and Anthropology, University of Göttingen, Göttingen, Germany.
Front Syst Neurosci. 2018 Mar 28;12:6. doi: 10.3389/fnsys.2018.00006. eCollection 2018.
Startle-induced locomotion is commonly used in research to monitor locomotor reactivity and its progressive decline with age or under various neuropathological conditions. A widely used paradigm is startle-induced negative geotaxis (SING), in which flies entrapped in a narrow column react to a gentle mechanical shock by climbing rapidly upwards. Here we combined manipulation of neuronal activity and splitGFP reconstitution across cells to search for brain neurons and putative circuits that regulate this behavior. We show that the activity of specific clusters of dopaminergic neurons (DANs) afferent to the mushroom bodies (MBs) modulates SING, and that DAN-mediated SING regulation requires expression of the DA receptor Dop1R1/Dumb, but not Dop1R2/Damb, in intrinsic MB Kenyon cells (KCs). We confirmed our previous observation that activating the MB α'β', but not αβ, KCs decreased the SING response, and we identified further MB neurons implicated in SING control, including KCs of the γ lobe and two subtypes of MB output neurons (MBONs). We also observed that co-activating the αβ KCs antagonizes α'β' and γ KC-mediated SING modulation, suggesting the existence of subtle regulation mechanisms between the different MB lobes in locomotion control. Overall, this study contributes to an emerging picture of the brain circuits modulating locomotor reactivity in that appear both to overlap and differ from those underlying associative learning and memory, sleep/wake state and stress-induced hyperactivity.
惊吓诱导的运动常用于研究中，以监测运动反应性及其随年龄增长或在各种神经病理条件下的逐渐下降。一种广泛使用的范式是惊吓诱导的负趋地性（SING），其中被困在狭窄柱体中的果蝇会通过快速向上攀爬对轻微机械冲击做出反应。在这里，我们结合了神经元活动的操纵和跨细胞的splitGFP重组，以寻找调节这种行为的脑神经元和假定的神经回路。我们表明，传入蘑菇体（MB）的特定多巴胺能神经元（DAN）簇的活动调节SING，并且DAN介导的SING调节需要在内在的MB肯扬细胞（KC）中表达多巴胺受体Dop1R1/Dumb，而不是Dop1R2/Damb。我们证实了我们之前的观察结果，即激活MBα'β' KC而不是αβ KC会降低SING反应，并且我们确定了更多与SING控制有关的MB神经元，包括γ叶的KC和两种MB输出神经元（MBON）亚型。我们还观察到，共同激活αβ KC会拮抗α'β'和γ KC介导的SING调节，这表明在运动控制中不同MB叶之间存在微妙的调节机制。总体而言，这项研究有助于形成一幅调节运动反应性的脑回路的新图景，这些脑回路似乎与那些参与联想学习和记忆、睡眠/觉醒状态以及应激诱导的多动的脑回路既有重叠又有不同。
