Mirabella Paul Nicholas, Fenselau Henning
Synaptic Transmission in Energy Homeostasis Group, Max Planck Institute for Metabolism Research, Cologne, Germany.
Center for Endocrinology, Diabetes and Preventive Medicine (CEDP), University Hospital Cologne, Cologne, Germany.
Nat Rev Endocrinol. 2023 Nov;19(11):639-654. doi: 10.1038/s41574-023-00885-6. Epub 2023 Sep 6.
Engineered neurobiological tools for the manipulation of cellular activity, such as chemogenetics and optogenetics, have become a cornerstone of modern neuroscience research. These tools are invaluable for the interrogation of the central control of metabolism as they provide a direct means to establish a causal relationship between brain activity and biological processes at the cellular, tissue and organismal levels. The utility of these methods has grown substantially due to advances in cellular-targeting strategies, alongside improvements in the resolution and potency of such tools. Furthermore, the potential to recapitulate endogenous cellular signalling has been enriched by insights into the molecular signatures and activity dynamics of discrete brain cell types. However, each modulatory tool has a specific set of advantages and limitations; therefore, tool selection and suitability are of paramount importance to optimally interrogate the cellular and circuit-based underpinnings of metabolic outcomes within the organism. Here, we describe the key principles and uses of engineered neurobiological tools. We also highlight inspiring applications and outline critical considerations to be made when using these tools within the field of metabolism research. We contend that the appropriate application of these biotechnological advances will enable the delineation of the central circuitry regulating systemic metabolism with unprecedented potential.
用于操纵细胞活动的工程化神经生物学工具，如化学遗传学和光遗传学，已成为现代神经科学研究的基石。这些工具对于探究代谢的中枢控制非常宝贵，因为它们提供了一种直接手段，能够在细胞、组织和机体水平上建立大脑活动与生物过程之间的因果关系。由于细胞靶向策略的进步以及这些工具在分辨率和效力方面的改进，这些方法的实用性已大幅提高。此外，对离散脑细胞类型的分子特征和活动动态的深入了解，丰富了重现内源性细胞信号传导的潜力。然而，每种调节工具都有一组特定的优点和局限性；因此，工具的选择和适用性对于在机体内最佳地探究代谢结果的细胞和基于回路的基础至关重要。在此，我们描述工程化神经生物学工具的关键原理和用途。我们还强调了鼓舞人心的应用，并概述了在代谢研究领域使用这些工具时需要考虑的关键因素。我们认为，这些生物技术进展的适当应用将以前所未有的潜力描绘出调节全身代谢的中枢神经回路。
