Optical Imaging Group, Institut für Neuroinformatik, Ruhr University Bochum, Bochum, Germany.
International Graduate School of Neuroscience, Ruhr University Bochum, Bochum, Germany.
Nat Commun. 2024 Sep 14;15(1):8078. doi: 10.1038/s41467-024-51861-1.
Response gain is a crucial means by which modulatory systems control the impact of sensory input. In the visual cortex, the serotonergic 5-HT receptor is key in such modulation. However, due to its expression across different cell types and lack of methods that allow for specific activation, the underlying network mechanisms remain unsolved. Here we optogenetically activate endogenous G protein-coupled receptor (GPCR) signaling of a single receptor subtype in distinct mouse neocortical subpopulations in vivo. We show that photoactivation of the 5-HT receptor pathway in pyramidal neurons enhances firing of both excitatory neurons and interneurons, whereas 5-HT photoactivation in parvalbumin interneurons produces bidirectional effects. Combined photoactivation in both cell types and cortical network modelling demonstrates a conductance-driven polysynaptic mechanism that controls the gain of visual input without affecting ongoing baseline levels. Our study opens avenues to explore GPCRs neuromodulation and its impact on sensory-driven activity and ongoing neuronal dynamics.
响应增益是调节系统控制感觉输入影响的关键手段。在视觉皮层中，5-羟色胺能 5-HT 受体在这种调节中起着关键作用。然而，由于其在不同细胞类型中的表达以及缺乏允许特定激活的方法，潜在的网络机制仍未解决。在这里，我们在体内对不同的小鼠新皮层亚群中的单个受体亚型的内源性 G 蛋白偶联受体 (GPCR) 信号进行光遗传学激活。我们表明，在锥体神经元中光激活 5-HT 受体途径会增强兴奋性神经元和中间神经元的放电，而在 Parvalbumin 中间神经元中光激活 5-HT 会产生双向作用。两种细胞类型的联合光激活和皮层网络建模表明，存在一种电导驱动的多突触机制，它控制视觉输入的增益，而不影响正在进行的基线水平。我们的研究为探索 GPCR 神经调节及其对感觉驱动活动和持续神经元动力学的影响开辟了途径。
