Abstract
The roles of serotonergic and noradrenergic signaling in nociceptive processing in the central nervous system are well known. However, dopaminergic signaling is also relevant to various physical functions, including nociception. The zona incerta is a subthalamic nucleus in which the A13 dopaminergic cell group resides, but how this A13 group affects nociceptive processing remains unknown. Recently, we showed that acute nociceptive stimuli rapidly induce the activity of A10 (ventral tegmental area) dopamine neurons via fiber photometry. In this study, we measured the activity of A13 dopaminergic neurons in response to acute nociceptive stimuli using the same system. Adeno-associated viruses (AAV-CAG-FLEX-G-CaMP6 and AAV-CAG-FLEX-mCherry) were unilaterally injected into the A13 site in transgenic mice carrying a dopamine transporter promotor-regulated Cre recombinase transgene to specifically introduce G-CaMP6/mCherry into A13 dopaminergic cell bodies through site-specific infection. We measured G-CaMP6/mCherry fluorescence intensity in the A13 site to acute nociceptive stimuli (pinch stimulus and heat stimulus). These stimuli significantly induced a rapid increase in G-CaMP6 fluorescence intensity, but non-nociceptive control stimuli did not. In contrast, mCherry fluorescence intensity was not significantly changed by nociceptive stimuli or non-nociceptive stimuli. Our finding is the first report to measure the activity of A13 dopaminergic neurons to aversive stimuli. A13 dopaminergic neurons project to the periaqueductal gray and the central nucleus of the amygdala, which are both well known as key regions in nociceptive processing. Therefore, together with our A10 study, our results indicate that A13 dopaminergic neurons play important roles in nociceptive processing.
Highlights
The zona incerta (ZI) is a subthalamic nucleus in the central nervous system (CNS) that contains dopaminergic neurons
* Correspondence: msmr9040psyg80@gmail.com 1Department of Physiology, Kagoshima University Graduate School of Medical and Dental Science, Kagoshima 890-8544, Japan Full list of author information is available at the end of the article neurons play roles in regulating various physical and mental functions, including nociception, in the CNS [3]
Specific expression of G-CaMP6/mCherry was confirmed in A13 dopaminergic neuronal soma (Fig. 1c, d)
Summary
The zona incerta (ZI) is a subthalamic nucleus in the central nervous system (CNS) that contains dopaminergic neurons. * Correspondence: msmr9040psyg80@gmail.com 1Department of Physiology, Kagoshima University Graduate School of Medical and Dental Science, Kagoshima 890-8544, Japan Full list of author information is available at the end of the article neurons play roles in regulating various physical and mental functions, including nociception, in the CNS [3]. We recently established that acute nociceptive stimuli rapidly increase the activity of ventral tegmental area (VTA, A10) DA neurons using a fiber
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
