1. Transient cAMP production drives rapid and sustained spiking in brainstem parabrachial neurons to suppress feeding.
- Author
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Singh Alvarado J, Lutas A, Madara JC, Isaac J, Lommer C, Massengill C, and Andermann ML
- Subjects
- Animals, Mice, Optogenetics, Cyclic AMP-Dependent Protein Kinases metabolism, Male, Glutamic Acid metabolism, Brain Stem physiology, Brain Stem metabolism, Mice, Inbred C57BL, Female, Parabrachial Nucleus physiology, Parabrachial Nucleus metabolism, Neurons physiology, Neurons metabolism, Cyclic AMP metabolism, Action Potentials physiology, Feeding Behavior physiology
- Abstract
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 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., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)- Published
- 2024
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