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 (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.
Competing Interests: Declaration of interests The authors declare no competing interests.
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