BNST Illuminated: Identifying and Manipulating Neuronal Circuits in Anorexia and Aversion

The inflammation-sensitive anterolateral bed nucleus of the stria terminalis (BNST), known for its involvement in negative affective states, has recently been shown to tap into canonical feeding pathways and to steer anorectic and aversive behaviour.

However, the projections and expression pattern of inflammation-sensitive BNST neurons and their relation to anorexia and aversion during disease are unknown.

In order to explore these BNST neurons, I aim to steer Cre-recombinase to activated neurons (FosTRAP) and induce stable expression of effector proteins specifically in inflammation-activated BNST neurons.

I will manipulate the activity of the TRAPed neurons using chemogenetics (1st year), map their projections, and use in vivo optogenetics to causally connect their projections to inflammation-induced anorexia and aversion (2nd and 3rd year).

I will create an expression map of this heterogenous region by using next generation in situ sequencing and multiplex ISH in combination with tracing from identified target sites (3rd year).

Finally, I will assess if my findings extend to models of real disease: Bacterial sepsis and viral influenza (4th year).

My research will profoundly advance our basic understanding of feeding and aversive circuits, with important implications for homeostatic feeding and maladaptive anorexia and aversion during inflammatory disease. It may also impact on other research areas on maladaptive feeding and food perception, such as anorexia nervosa.