School of Clinical Sciences, Faculty of Health, Queensland University of Technology, 2 George Street, Brisbane 4000, QLD, Australia.
UQ Centre for Clinical Research, Faculty of Medicine, University of Queensland, Building 71/918 Royal Brisbane and Women's Hospital Campus, Herston 4029, QLD, Australia.
Rev Neurosci. 2022 Sep 5;34(3):295-311. doi: 10.1515/revneuro-2022-0072. Print 2023 Apr 25.
Disordered eating can underpin a number of debilitating and prevalent chronic diseases, such as obesity. Broader advances in psychopharmacology and biology have motivated some neuroscientists to address diet-induced obesity through reductionist, pre-clinical eating investigations on the rodent brain. Specifically, chemogenetic and optogenetic methods developed in the 21st century allow neuroscientists to perform , region-specific/projection-specific/promoter-specific circuit manipulations and immediately assess the impact of these manipulations on rodent feeding. These studies are able to rigorously conclude whether a specific neuronal population regulates feeding behaviour in the hope of eventually developing a mechanistic neuroanatomical map of appetite regulation. However, an artificially stimulated/inhibited rodent neuronal population that changes feeding behaviour does not necessarily represent a pharmacological target for treating eating disorders in humans. Chemogenetic/optogenetic findings must therefore be triangulated with the array of theories that contribute to our understanding of appetite. The objective of this review is to provide a wide-ranging discussion of the limitations of chemogenetic/optogenetic circuit manipulation experiments in rodents that are used to investigate appetite. Stepping into and outside of medical science epistemologies, this paper draws on philosophy of science, nutrition, addiction biology and neurophilosophy to prompt more integrative, transdisciplinary interpretations of chemogenetic/optogenetic appetite data. Through discussing the various technical and epistemological limitations of these data, we provide both an overview of chemogenetics and optogenetics accessible to non-neuroscientist obesity researchers, as well as a resource for neuroscientists to expand the number of lenses through which they interpret their circuit manipulation findings.
饮食失调会导致许多使人衰弱且普遍存在的慢性疾病，例如肥胖症。精神药理学和生物学的广泛进步促使一些神经科学家通过对啮齿动物大脑进行简化的、临床前的饮食研究来解决饮食引起的肥胖问题。具体来说，21 世纪开发的化学遗传学和光遗传学方法使神经科学家能够进行特定区域/特定投射/特定启动子的回路操作，并立即评估这些操作对啮齿动物进食的影响。这些研究能够严格得出是否特定神经元群体调节进食行为的结论，以期最终开发出食欲调节的机制神经解剖学图谱。然而，改变进食行为的人工刺激/抑制的啮齿动物神经元群体并不一定代表治疗人类饮食失调的药理学靶点。因此，必须将化学遗传学/光遗传学发现与有助于我们理解食欲的各种理论结合起来。本综述的目的是广泛讨论用于研究食欲的啮齿动物化学遗传学/光遗传学回路操作实验的局限性。本文从医学科学认识论的角度出发，借鉴了哲学、营养学、成瘾生物学和神经哲学，以促使对化学遗传学/光遗传学食欲数据进行更具综合性、跨学科的解释。通过讨论这些数据的各种技术和认识论限制，我们为非神经科学家肥胖研究人员提供了化学遗传学和光遗传学的概述，同时也为神经科学家提供了一个资源，以扩大他们解释回路操作发现的视角。
