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Publication : Pain modulates dopamine neurons via a spinal-parabrachial-mesencephalic circuit.

First Author  Yang H Year  2021
Journal  Nat Neurosci Volume  24
Issue  10 Pages  1402-1413
PubMed ID  34373644 Mgi Jnum  J:323967
Mgi Id  MGI:7263127 Doi  10.1038/s41593-021-00903-8
Citation  Yang H, et al. (2021) Pain modulates dopamine neurons via a spinal-parabrachial-mesencephalic circuit. Nat Neurosci 24(10):1402-1413
abstractText  Pain decreases the activity of many ventral tegmental area (VTA) dopamine (DA) neurons, yet the underlying neural circuitry connecting nociception and the DA system is not understood. Here we show that a subpopulation of lateral parabrachial (LPB) neurons is critical for relaying nociceptive signals from the spinal cord to the substantia nigra pars reticulata (SNR). SNR-projecting LPB neurons are activated by noxious stimuli and silencing them blocks pain responses in two different models of pain. LPB-targeted and nociception-recipient SNR neurons regulate VTA DA activity directly through feed-forward inhibition and indirectly by inhibiting a distinct subpopulation of VTA-projecting LPB neurons thereby reducing excitatory drive onto VTA DA neurons. Correspondingly, ablation of SNR-projecting LPB neurons is sufficient to reduce pain-mediated inhibition of DA release in vivo. The identification of a neural circuit conveying nociceptive input to DA neurons is critical to our understanding of how pain influences learning and behavior.
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