Brain integration and processing of ingestive signals

After meal consumption, the brain evaluates the value of its contents and relays this information via neuronal circuits connecting the periphery with the brain (1,2). Although the brain is now recognised as the master regulator of appetite and energy homeostasis, our understanding of how and which circuits decode the post-ingestive nutritional and hedonic value of food from the periphery to the brain remain largely unknown. The advent of new genetic technologies now provide a powerful means by which to unravel the contribution of discrete neurons to appetitive behaviour and systemic energy balance with unprecedented spatial and temporal resolution (2,3).

The host laboratories have started to phenotype the neurones in the caudal brainstem, an important brain region that serves as a first relay station for peripherally generated signals entering the brain (4,5). Published (2,4) and unpublished data suggest that segregated brainstem circuits selectively respond to distinct nutritional and non-nutritional signals and transmit this information to multiple second order brain regions so that the brain can compute and attribute motivational valence. The overarching aim of this project is to resolve these circuits and characterise them at the genetic, structural and functional level.
To this end, the student will receive training in using the latest genetic technologies available that will allow him/her to genetically tag distinct brainstem neurons after they have responded to the nutritional and non-nutritional signals. This permanent genetic tagging will then allow the student to identify the neurons and their connections, record their activity during normal behaviour and selectively activate/inhibit them to interrogate their significance to behaviour.

Resolving these circuits will not only expand our understanding of how ingestive behaviour is regulated, but it will also inform design of novel medications with improved efficacy and patient compliance.