Involvement of supralemniscal nucleus (B9) 5-HT neuronal system in nociceptive processing: a fiber photometry study

• Published in: Molecular brain Vol. 13; no. 1; p. 14
• Main Authors: Moriya, Shunpei, Yamashita, Akira, Masukawa, Daiki, Kambe, Yuki, Sakaguchi, Junichi, Setoyama, Honami, Yamanaka, Akihiro, Kuwaki, Tomoyuki
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 31.01.2020; BioMed Central; BMC
• Subjects: Animals; B9 5-HT cell group; Dependovirus - genetics; Dorsal horn; Efferent Pathways - physiology; Fiber Optic Technology - methods; Fiber optics; Fiber photometry; Fluorescence; G-CaMP6; Genes, Reporter; Genes, Synthetic; Genetic engineering; Green Fluorescent Proteins - genetics; Heat stimuli; Hot Temperature; Hydroxylases; Laboratory animals; Locus coeruleus; Locus Coeruleus - physiology; Luminescent Proteins - analysis; Luminescent Proteins - genetics; Medulla oblongata; Mice; Mice, Transgenic; Neurons; Nociception; Nociception - physiology; Pain; Pain management; Pain perception; Penicillin G; Phenols (Class of compounds); Photometry; Photometry - methods; Pons - physiology; Pressure; Reaction Time; Recombinant Fusion Proteins - genetics; Red Fluorescent Protein; Serotonergic Neurons - chemistry; Serotonergic Neurons - physiology; Serotonin; Tetracyclines; Third generation wireless technology; Trans-Activators; Transgenic animals; Transgenic mice; Tryptophan; Tryptophan hydroxylase; Tryptophan Hydroxylase - genetics; Ventral tegmental area; Ventral Tegmental Area - physiology; Ventral tegmentum; Japan; United States > US; Nociception; B9 5-HT cell group; Fiber photometry; TPH2-tTA mice; Ventral tegmental area; G-CaMP6; Locus coeruleus
• ISSN: 1756-6606; 1756-6606
• DOI: 10.1186/s13041-020-0553-1

Nociception is important perception that has harmful influence on daily life of humans. As to main pain management system, some descending pathways are called descending antinociceptive systems (DAS). As main pathways of DAS, it is well known that dorsal raphe (B6/B7) - rostral ventromedial medulla (B3) - spinal dorsal horn includes serotonergic system. However, possible role of supralemniscal (B9) serotonin (5-HT) cell group in pain management is still open question. In this study, we measured activities of B9 5-HT neuronal cell bodies and B9 5-HT neuron-derived axons located in the locus coeruleus (LC) and ventral tegmental area (VTA), which are also main players of pain management, using fiber photometry system. We introduced the G-CaMP6 in B9 5-HT neurons using transgenic mice carrying a tetracycline-controlled transactivator transgene (tTA) under the control of a tryptophan hydroxylase-2 (TPH2) promoter and site-specific injection of adeno associated virus (AAV-TetO(3G)-G-CaMP6). After confirmation of specific expression of G-CaMP6 in the target population, G-CaMP6 fluorescence intensity in B9 group and LC/VTA groups was measured in awake mice exposed to acute tail pinch and heat stimuli. G-CaMP6 fluorescence intensity rapidly increased by both stimuli in all groups, but not significantly reacted by nonnociceptive control stimuli. The present results clearly indicate that acute nociceptive stimuli cause a rapid increase in the activities of B9-LC/B9-VTA 5-HTergic pathways, suggesting that B9 5-HT neurons play important roles in nociceptive processing.