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

Abstract

AbstractBrief 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 (PBNGlut) regulate sustained brain states such as pain, and express Gs-coupled GPCRs that increase cAMP signaling. We asked whether cAMP directly influences PBNGlutexcitability and behavior. Both brief tail shocks and brief optogenetic stimulation of cAMP production in PBNGlutneurons drove minutes-long suppression of feeding. This suppression matched the duration of prolonged elevations in cAMP, Protein Kinase A (PKA), and calcium activityin vivoandin vitro.Shortening this elevation in cAMP reduced the duration of feeding suppression following tail shocks. cAMP elevations in PBNGlutneurons rapidly lead to sustained increases in action potential firing via PKA-dependent mechanisms. Thus, molecular signaling in PBNGlutneurons helps prolong neural activity and behavioral states evoked by brief, salient bodily stimuli.