Laboratorio de Genética del Comportamiento, Fundación Instituto Leloir, IIBBA-CONICET, Av. Patricias Argentinas 435, Buenos Aires 1405-BWE, Argentina.
Laboratorio de Genética del Comportamiento, Fundación Instituto Leloir, IIBBA-CONICET, Av. Patricias Argentinas 435, Buenos Aires 1405-BWE, Argentina.
Curr Biol. 2020 Dec 21;30(24):5040-5048.e5. doi: 10.1016/j.cub.2020.09.057. Epub 2020 Oct 15.
Behavioral outputs arise as a result of highly regulated yet flexible communication among neurons. The Drosophila circadian network includes 150 neurons that dictate the temporal organization of locomotor activity; under light-dark (LD) conditions, flies display a robust bimodal pattern. The pigment-dispersing factor (PDF)-positive small ventral lateral neurons (sLNv) have been linked to the generation of the morning activity peak (the "M cells"), whereas the Cryptochrome (CRY)-positive dorsal lateral neurons (LNds) and the PDF-negative sLNv are necessary for the evening activity peak (the "E cells") [1, 2]. While each group directly controls locomotor output pathways [3], an interplay between them along with a third dorsal cluster (the DN1ps) is necessary for the correct timing of each peak and for adjusting behavior to changes in the environment [4-7]. M cells set the phase of roughly half of the circadian neurons (including the E cells) through PDF [5, 8-10]. Here, we show the existence of synaptic input provided by the evening oscillator onto the M cells. Both structural and functional approaches revealed that E-to-M cell connectivity changes across the day, with higher excitatory input taking place before the day-to-night transition. We identified two different neurotransmitters, acetylcholine and glutamate, released by E cells that are relevant for robust circadian output. Indeed, we show that acetylcholine is responsible for the excitatory input from E cells to M cells, which show preferential responsiveness to acetylcholine during the evening. Our findings provide evidence of an excitatory feedback between circadian clusters and unveil an important plastic remodeling of the E cells' synaptic connections.
行为输出是神经元之间高度调节但灵活的通讯的结果。果蝇的生物钟网络包括 150 个神经元，它们决定着运动活动的时间组织；在光暗（LD）条件下，果蝇表现出强烈的双峰模式。色素扩散因子（PDF）阳性的小腹外侧神经元（sLNv）与早晨活动高峰（“M 细胞”）的产生有关，而隐色素（CRY）阳性的外侧背神经元（LNds）和 PDF 阴性的 sLNv 是晚上活动高峰（“E 细胞”）所必需的[1,2]。虽然每个群体都直接控制着运动输出途径[3]，但它们之间的相互作用以及第三个背侧簇（DN1ps）对于每个高峰的正确定时和调整行为以适应环境变化是必要的[4-7]。M 细胞通过 PDF 为大约一半的生物钟神经元（包括 E 细胞）设定相位[5,8-10]。在这里，我们展示了晚上振荡器对 M 细胞提供的突触输入的存在。结构和功能方法都表明，E 细胞到 M 细胞的连接在一天中发生变化，在白天到黑夜的过渡之前，兴奋性输入增加。我们确定了两种不同的神经递质，乙酰胆碱和谷氨酸，由 E 细胞释放，它们与强大的生物钟输出有关。事实上，我们表明，乙酰胆碱是 E 细胞到 M 细胞的兴奋性输入的原因，M 细胞在晚上对乙酰胆碱表现出优先反应性。我们的发现为生物钟簇之间的兴奋性反馈提供了证据，并揭示了 E 细胞突触连接的重要可塑性重塑。
