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Brainstem somatostatin-expressing cells control the emotional regulation of pain behavior

Nanci Winke, Frank Aby, Daniel Jercog, Grivet Zoé, Delphine Girard, Marc Landry, Laia Castell, Emmanuel Valjent, Stephane Valerio, View ORCID ProfilePascal Fossat, View ORCID ProfileCyril Herry
doi: https://doi.org/10.1101/2022.01.20.476899
Nanci Winke
1Univ. Bordeaux, Neurocentre Magendie, U1215, 146 Rue Léo-Saignat, 33077 Bordeaux, France
2INSERM, Neurocentre Magendie, U1215, 146 Rue Léo-Saignat, 33077 Bordeaux, France
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Frank Aby
3Institut des maladies neurodégénératives (IMN, CNRS UMR 5293), 146 Rue Léo-Saignat, 33077 Bordeaux, France
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Daniel Jercog
1Univ. Bordeaux, Neurocentre Magendie, U1215, 146 Rue Léo-Saignat, 33077 Bordeaux, France
2INSERM, Neurocentre Magendie, U1215, 146 Rue Léo-Saignat, 33077 Bordeaux, France
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Grivet Zoé
3Institut des maladies neurodégénératives (IMN, CNRS UMR 5293), 146 Rue Léo-Saignat, 33077 Bordeaux, France
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Delphine Girard
1Univ. Bordeaux, Neurocentre Magendie, U1215, 146 Rue Léo-Saignat, 33077 Bordeaux, France
2INSERM, Neurocentre Magendie, U1215, 146 Rue Léo-Saignat, 33077 Bordeaux, France
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Marc Landry
3Institut des maladies neurodégénératives (IMN, CNRS UMR 5293), 146 Rue Léo-Saignat, 33077 Bordeaux, France
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Laia Castell
4IGF, Montpellier, CNRS, INSERM, 34094 Montpellier, France
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Emmanuel Valjent
4IGF, Montpellier, CNRS, INSERM, 34094 Montpellier, France
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Stephane Valerio
1Univ. Bordeaux, Neurocentre Magendie, U1215, 146 Rue Léo-Saignat, 33077 Bordeaux, France
2INSERM, Neurocentre Magendie, U1215, 146 Rue Léo-Saignat, 33077 Bordeaux, France
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Pascal Fossat
3Institut des maladies neurodégénératives (IMN, CNRS UMR 5293), 146 Rue Léo-Saignat, 33077 Bordeaux, France
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  • ORCID record for Pascal Fossat
Cyril Herry
1Univ. Bordeaux, Neurocentre Magendie, U1215, 146 Rue Léo-Saignat, 33077 Bordeaux, France
2INSERM, Neurocentre Magendie, U1215, 146 Rue Léo-Saignat, 33077 Bordeaux, France
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  • For correspondence: cyril.herry@inserm.fr
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Abstract

In mammals, threat-related behavior is typically induced by a noxious physical stressor and is associated with a broad range of behavioral responses such as freezing and avoidance. These behavioral responses are associated with the regulation of pain responses allowing individuals to cope with noxious stimuli. Whereas the structures and mechanisms involved in pain behavior are well documented, little is known about the precise neuronal circuits mediating the emotional regulation of pain behavior. Here we used a combination of behavioral, anatomical, optogenetic, and electrophysiological approaches to show that somatostatin-expressing neurons in the ventrolateral periaqueductal gray matter (vlPAG SST cells) promote antinociceptive responses during the presentation of conditioned stimuli (CS) predicting footshocks. Whereas the optogenetic inhibition of vlPAG SST cells during CS presentation promoted analgesia, their optogenetic activation reduced analgesia by potentiating pain responses in the spinal cord through a relay in the rostral ventromedial medulla (RVM). Together these results identify a brainstem circuit composed of vlPAG SST cells specifically projecting to the RVM and mediating fear conditioned analgesia (FCA) to regulate pain responses during threatful situations.

Competing Interest Statement

The authors have declared no competing interest.

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Posted January 22, 2022.
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Brainstem somatostatin-expressing cells control the emotional regulation of pain behavior
Nanci Winke, Frank Aby, Daniel Jercog, Grivet Zoé, Delphine Girard, Marc Landry, Laia Castell, Emmanuel Valjent, Stephane Valerio, Pascal Fossat, Cyril Herry
bioRxiv 2022.01.20.476899; doi: https://doi.org/10.1101/2022.01.20.476899
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Brainstem somatostatin-expressing cells control the emotional regulation of pain behavior
Nanci Winke, Frank Aby, Daniel Jercog, Grivet Zoé, Delphine Girard, Marc Landry, Laia Castell, Emmanuel Valjent, Stephane Valerio, Pascal Fossat, Cyril Herry
bioRxiv 2022.01.20.476899; doi: https://doi.org/10.1101/2022.01.20.476899

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