Invited Review - Chemical, Optogenetic and Pharmacosynthetic Approaches to Acutely Control Feeding: What's So Spatial About Our Methods?

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Since 1954, many laboratories have used intracranial microinjection techniques to acutely control feeding behavior in experimental animals. Few, however, have documented the locations of their effective and ineffective injection sites within the brain, and even fewer have plotted the locations of these sites within a neuroanatomical reference atlas space. Without such an anatomical framework, it is a formidable challenge to be certain about the neuroanatomical substrates affected by experimentally delivered chemicals to control feeding. A lack of anatomical resolution in such experiments has limited their utility. However, publishing maps from legacy datasets of previously unreported histology could help the scientific community extract meaningful data from otherwise hard-to-interpret studies. In this review, a brief history of central microinjection studies examining acute feeding control is first presented. In particular, studies that include published histology of injection sites mapped to a reference atlas are highlighted, and the lasting value of these older studies is emphasized. I then discuss how using a few simple procedures, behavioral neuroscientists studying feeding control can use atlas-based mapping techniques to bring their microinjection studies into anatomical registration with those of other laboratories. To illustrate this concept, I show how mapping injection sites within the Swanson rat brain atlas will allow scientists to understand the architecture of the affected regions situated beneath their injections. This is because a richly annotated and curated dataset of rat brain connections within the Swanson atlas reference space is available online, which can be placed in direct register with any feeding control sites mapped within this atlas. Finally, similar mapping strategies can be employed for studies using recently developed optogenetic and chemicogenetic methods, particularly within the context of activated neuron populations in the mouse brain. It is anticipated that atlas-based mapping will be a critical step towards community-based sharing of data on feeding control circuits, and will accelerate our understanding of structure-function relationships in the brain for mammalian models of obesity and metabolic disorders.

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