Pain modulates dopamine neurons via a spinal–parabrachial–mesencephalic circuit
- Resource Type
- Authors
- Johannes W. de Jong; Hui Gong; Stephan Lammel; Ignas Cerniauskas; James R. Peck; Hongbin Yang; Byung Kook Lim; Howard L. Fields
- Source
- Nat Neurosci
- Subject
- Male
Nociception
Pain
Optogenetics
Biology
Article
Mice
Mesencephalon
Dopamine
Neural Pathways
medicine
Noxious stimulus
Biological neural network
Animals
Pain Management
Neurons
Brain Mapping
Behavior, Animal
Dopaminergic Neurons
General Neuroscience
Ventral Tegmental Area
Parabrachial Nucleus
Spinal cord
Mice, Inbred C57BL
Substantia Nigra
Ventral tegmental area
medicine.anatomical_structure
Spinal Cord
nervous system
Excitatory postsynaptic potential
Neuroscience
medicine.drug
- Language
- ISSN
- 1546-1726
1097-6256
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.