Lateral preoptic area glutamate neurons relay nociceptive information to the ventral tegmental area
David J. Barker,
Shiliang Zhang,
Huiling Wang,
David J. Estrin,
Jorge Miranda-Barrientos,
Bing Liu,
Rucha J. Kulkarni,
Junia Lara de Deus,
Marisela Morales
Affiliations
David J. Barker
Integrative Neuroscience Branch, Neuronal Networks Section, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD 21224, USA
Shiliang Zhang
Confocal and Electron Microscopy Core, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD 21224, USA
Huiling Wang
Integrative Neuroscience Branch, Neuronal Networks Section, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD 21224, USA
David J. Estrin
Integrative Neuroscience Branch, Neuronal Networks Section, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD 21224, USA
Jorge Miranda-Barrientos
Integrative Neuroscience Branch, Neuronal Networks Section, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD 21224, USA
Bing Liu
Integrative Neuroscience Branch, Neuronal Networks Section, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD 21224, USA
Rucha J. Kulkarni
Integrative Neuroscience Branch, Neuronal Networks Section, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD 21224, USA
Junia Lara de Deus
Integrative Neuroscience Branch, Neuronal Networks Section, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD 21224, USA
Marisela Morales
Integrative Neuroscience Branch, Neuronal Networks Section, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD 21224, USA; Corresponding author
Summary: The ventral tegmental area (VTA) has been proposed to play a role in pain, but the brain structures modulating VTA activity in response to nociceptive stimuli remain unclear. Here, we demonstrate that the lateral preoptic area (LPO) glutamate neurons relay nociceptive information to the VTA. These LPO glutamatergic neurons synapsing on VTA neurons respond to nociceptive stimulation and conditioned stimuli predicting nociceptive stimulation and also mediate aversion. In contrast, LPO GABA neurons synapsing in the VTA mediate reward. By ultrastructural quantitative synaptic analysis, ex vivo electrophysiology, and functional neuroanatomy we identify a complex circuitry between LPO glutamatergic and GABAergic neurons and VTA dopaminergic, GABAergic, and glutamatergic neurons. We conclude that LPO glutamatergic neurons play a causal role in the processing of nociceptive stimuli and in relaying information about nociceptive stimuli. The pathway from LPO glutamatergic neurons to the VTA represents an unpredicted interface between peripheral nociceptive information and the limbic system.
