RESUMEN
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.
Asunto(s)
Potenciales de Acción , AMP Cíclico , Conducta Alimentaria , Neuronas , Núcleos Parabraquiales , Animales , Núcleos Parabraquiales/fisiología , Núcleos Parabraquiales/metabolismo , Neuronas/fisiología , Neuronas/metabolismo , AMP Cíclico/metabolismo , Ratones , Potenciales de Acción/fisiología , Conducta Alimentaria/fisiología , Optogenética , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Masculino , Ácido Glutámico/metabolismo , Tronco Encefálico/fisiología , Tronco Encefálico/metabolismo , Ratones Endogámicos C57BL , FemeninoRESUMEN
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.