Competition between stochastic neuropeptide signals calibrates the rate of satiation
bioRxiv, ISSN: 2692-8205
2023
- 1Mentions
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Most Recent News
Dissociable hindbrain GLP1R circuits for satiety and aversion
Nature, Published online: 10 July 2024; doi:10.1038/s41586-024-07685-6 The neural circuits in the hindbrain that link satiety and aversion are shown to be separate, raising the possibility of developing obesity drugs without the common side effects of nausea and vomiting.
Article Description
We investigated how transmission of hunger- and satiety-promoting neuropeptides, NPY and αMSH, is integrated at the level of intracellular signaling to control feeding. Receptors for these peptides use the second messenger cAMP, but the messenger’s spatiotemporal dynamics and role in energy balance are controversial. We show that AgRP axon stimulation in the paraventricular hypothalamus evokes probabilistic and spatially restricted NPY release that triggers stochastic cAMP decrements in downstream MC4R-expressing neurons (PVH). Meanwhile, POMC axon stimulation triggers stochastic, αMSH-dependent cAMP increments. NPY and αMSH competitively control cAMP, as reflected by hunger-state-dependent differences in the amplitude and persistence of cAMP transients evoked by each peptide. During feeding bouts, elevated αMSH release and suppressed NPY release cooperatively sustain elevated cAMP in PVH neurons, thereby potentiating feeding-related excitatory inputs and promoting satiation across minutes. Our findings highlight how state-dependent integration of opposing, quantal peptidergic events by a common biochemical target calibrates energy intake.
Bibliographic Details
Cold Spring Harbor Laboratory
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