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 (PBNGlut) neurons regulate sustained brain states such as pain and express Gs-coupled GPCRs that increase cAMP signaling. We asked whether cAMP in PBNGlut neurons directly influences their excitability and effects on behavior. Both brief tail shocks and brief optogenetic stimulation of cAMP production in PBNGlut neurons drove minutes-long suppression of feeding. This suppression matched the duration of prolonged elevations in cAMP, protein kinase A (PKA) activity, and calcium activity in vivo and ex vivo, as well as sustained, PKA-dependent increases in action potential firing ex vivo. Shortening this elevation in cAMP reduced the duration of feeding suppression following tail shocks. Thus, molecular signaling in PBNGlut neurons helps prolong neural activity and behavioral states evoked by brief, salient bodily stimuli. •Transient cAMP production drives minutes-long spiking in parabrachial nucleus neurons•Translation of cAMP to spiking relies on PKA-dependent and independent mechanisms•Shock-evoked cAMP is necessary for prolonged suppression of feeding•cAMP signaling extends behavioral responses to threat stimuli from seconds to minutes Singh Alvarado, Lutas, and colleagues use optical tools to demonstrate that persistent cAMP signaling directly couples to neuronal activity in the parabrachial nucleus to drive sustained suppression of feeding. The results suggest that cAMP produced by transient GPCR activation can extend the timescale of neuronal activity from seconds to minutes.