Advanced neurobiological tools to interrogate metabolism.

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.