Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.11.088773v1?rss=1 Authors: Sabatini, P. V., Henriette Frikke-Schmidt, H., Arthurs, J., Gordian, D., Patel, A., Adams, J. M., Wang, J., Beck Jorgensen, S., Olson, D. P., Palmiter, R. D., Myers, M. G., Seeley, R. J. Abstract: To determine the function and mechanisms of action for hindbrain neurons that express GFRAL, the receptor for the anorexigenic peptide, GDF-15, we generated GfralCre and conditional GfralCreERT mice. While signals of infection or pathophysiologic states (rather than meal ingestion) stimulate GFRAL neurons, the artificial activation of GfralCre-expressing neurons inhibited feeding, decreased gastric emptying, and promoted a conditioned taste aversion (CTA). Additionally, activation of the smaller population of GFRAL neurons captured by the GfralCreERT allele decreased gastric emptying and produced a CTA without suppressing food intake, suggesting that GFRAL neurons primarily modulate gastric physiology and stimulate aversive responses. GFRAL neurons most strongly innervated the parabrachial nucleus (PBN), where they targeted CGRP-expressing (CGRPPBN) neurons. Silencing CGRPPBN neurons abrogated the aversive and anorexic effects of GDF-15. These findings suggest that GFRAL neurons link non-meal-associated, pathophysiologic signals to the aversive suppression of nutrient uptake and absorption. Copy rights belong to original authors. Visit the link for more info