The limitations of investigating appetite through circuit manipulations: are we biting off more than we can chew?

Joshua Wang; Kate Beecher; Fatemeh Chehrehasa; Hayley Moody

doi:10.1515/revneuro-2022-0072

The limitations of investigating appetite through circuit manipulations: are we biting off more than we can chew?

Rev Neurosci. 2022 Sep 5;34(3):295-311. doi: 10.1515/revneuro-2022-0072. Print 2023 Apr 25.

Authors

Joshua Wang¹, Kate Beecher², Fatemeh Chehrehasa³, Hayley Moody⁴

Affiliations

¹ School of Clinical Sciences, Faculty of Health, Queensland University of Technology, 2 George Street, Brisbane 4000, QLD, Australia.
² 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.
³ School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, 2 George Street, Brisbane 4000, QLD, Australia.
⁴ Queensland University of Technology, 2 George Street, Brisbane 4000, QLD, Australia.

PMID: 36054842
DOI: 10.1515/revneuro-2022-0072

Abstract

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 in vivo, 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.

Keywords: appetite; chemogenetic; circuit manipulation; obesity; optogenetic.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Appetite* / physiology
Brain / physiology
Humans
Neurons
Obesity
Optogenetics* / methods
Rodentia