Transient cAMP production drives rapid and sustained spiking in brainstem parabrachial neurons to suppress feeding.

Brief stimuli can trigger longer lasting brain states. G protein-coupled receptors (GPCRs) could help sustain such states by coupling slow-timescale molecular signals to neuronal excitability. Brainstem parabrachial nucleus glutamatergic neurons (PBN ^Glut ) regulate sustained brain states such as pain, and express G _s -coupled GPCRs that increase cAMP signaling. We asked whether cAMP directly influences PBN ^Glut excitability and behavior. Both brief tail shocks and brief optogenetic stimulation of cAMP production in PBN ^Glut neurons drove minutes-long suppression of feeding. This suppression matched the duration of prolonged elevations in cAMP, Protein Kinase A (PKA), and calcium activity in vivo and in vitro. Shortening this elevation in cAMP reduced the duration of feeding suppression following tail shocks. cAMP elevations in PBN ^Glut neurons rapidly lead to sustained increases in action potential firing via PKA-dependent mechanisms. Thus, molecular signaling in PBN ^Glut neurons helps prolong neural activity and behavioral states evoked by brief, salient bodily stimuli.