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Publication : Divergent brainstem opioidergic pathways that coordinate breathing with pain and emotions.

First Author  Liu S Year  2022
Journal  Neuron Volume  110
Issue  5 Pages  857-873.e9
PubMed ID  34921781 Mgi Jnum  J:325015
Mgi Id  MGI:7282317 Doi  10.1016/j.neuron.2021.11.029
Citation  Liu S, et al. (2022) Divergent brainstem opioidergic pathways that coordinate breathing with pain and emotions. Neuron 110(5):857-873.e9
abstractText  Breathing can be heavily influenced by pain or internal emotional states, but the neural circuitry underlying this tight coordination is unknown. Here we report that Oprm1 (mu-opioid receptor)-expressing neurons in the lateral parabrachial nucleus (PBL) are crucial for coordinating breathing with affective pain in mice. Individual PBL(Oprm1) neuronal activity synchronizes with breathing rhythm and responds to noxious stimuli. Manipulating PBL(Oprm1) activity directly changes breathing rate, affective pain perception, and anxiety. Furthermore, PBL(Oprm1) neurons constitute two distinct subpopulations in a "core-shell" configuration that divergently projects to the forebrain and hindbrain. Through non-overlapping projections to the central amygdala and pre-Botzinger complex, these two subpopulations differentially regulate breathing, affective pain, and negative emotions. Moreover, these subsets form recurrent excitatory networks through reciprocal glutamatergic projections. Together, our data define the divergent parabrachial opioidergic circuits as a common neural substrate that coordinates breathing with various sensations and behaviors such as pain and emotional processing.
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