| Autor: |
Mai Iwasaki, Arthur Lefevre, Ferdinand Althammer, Olga Łąpieś, Louis Hilfiger, Damien Kerspern, Meggane Melchior, Stephanie Küppers, Quirin Krablicher, Ryan Patwell, Sabine C Herpertz, Beate Ditzen, Kai Schönig, Dusan Bartsch, Javier E. Stern, Pascal Darbon, Valery Grinevich, Alexandre Charlet |
| Rok vydání: |
2022 |
| DOI: |
10.1101/2022.02.23.481531 |
| Popis: |
The hypothalamic neuropeptide, oxytocin (OT), exerts prominent analgesic effects via central and peripheral action. Here we discovered a novel subset of OT neurons whose projections preferentially terminate on OT receptor (OTR)-expressing neurons in the ventrolateral periaqueductal gray (vlPAG). Using a newly generated line of transgenic rats (OTR-IRES-Cre), we determined that most of the vlPAG OTR expressing cells being targeted by OT projections are GABAergic in nature. Both optogenetically-evoked axonal OT release in the vlPAG as well as chemogenetic activation of OTR vlPAG neurons results in a long-lasting overall increase of vlPAG neuronal activity. This then leads to an indirect suppression of sensory neuron activity in the spinal cord and strong analgesia. Finally, we describe a novel OT→vlPAG→spinal cord circuit that seems critical for analgesia in the context of both inflammatory and neuropathic pain.Highlights- We generated a new transgenic knock-in rat line (OTR-IRES-Cre)- A distinct parvOT neuronal population projects to vlPAG but not the SON or spinal cord- OT excites vlPAG OTR neurons which indirectly inhibit SC WDR neurons- This novel parvOT→vlPAG→SC pathway alleviates nociception but not the affective component of pain |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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