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

Summary

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 (PBN^Glut) neurons regulate sustained brain states such as pain and express G_s-coupled GPCRs that increase cAMP signaling. We asked whether cAMP in PBN^Glut neurons directly influences their excitability and effects on 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) 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 PBN^Glut neurons helps prolong neural activity and behavioral states evoked by brief, salient bodily stimuli.