ORIGINAL RESEARCH article
Front. Neuroanat.
Volume 19 - 2025 | doi: 10.3389/fnana.2025.1600026
Impaired modulation of the trigeminal caudal nucleus by the locus coeruleus in diabetic mice: The role of GABAergic and glycinergic neurons
Provisionally accepted
- 1Department of Anatomy, Histology and Neuroscience, Faculty of Medicine, Autonomous University of Madrid, Madrid, Madrid, Spain
- 2Facultad de Ciencias de la Salud, Universidad Francisco de Vitoria, Pozuelo de Alarcón, Madrid, Spain
- 3Facultad de Medicina, Universidad Francisco de Vitoria, Pozuelo de Alarcón, Madrid, Spain
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
The trigeminal system plays a crucial role in processing somatosensory information, and its modulation is essential for maintaining sensory homeostasis.This study investigates the inhibitory modulation of trigeminal somatosensory responses by the locus coeruleus (LC), which is involved in numerous cognitive and physiological functions. Previous electrophysiological investigations have shown a diminished ability of the LC to inhibit somatosensory responses in the caudalis division of the spinal trigeminal nucleus (Sp5C) in diabetic mice. We hypothesize that γ-Amino-butyric acid (GABA)ergic and glycinergic neurons in the Sp5C may also participate in modulatory action from the LC. Using unit recordings in isoflurane anesthetized control and streptozotocin-induced diabetic mice, we examined the effect of LC electrical stimulation on GABAergic and glycinergic neurons, while monitoring trigeminal somatosensory responses to vibrissal stimulation. Local applications of bicuculline or strychnine (antagonists of GABAergic and glycinergic receptors, respectively) demonstrated that GABAergic and glycinergic neurons are under the control of noradrenergic projections from the LC by activation of α1 and α2 noradrenergic receptors, respectively. In diabetic mice, the functionality of these inhibitory circuits was reduced, contributing to the observed deficiency in LC-mediated sensory modulation and likely contributing to generation of neuropathic pain.Immunohistochemical experiments confirmed the presence of α1 and α2 noradrenergic receptors in GABAergic and glycinergic neurons that were altered in diabetic mice. In conclusion, the LC modulation exerted on the somatosensory responses in the Sp5C is not only through noradrenergic receptors on glutamatergic projection neurons but also exerts its control through projections to inhibitory interneurons.
Keywords: noradrenergic receptors, GABAergic Neurons, glycinergic neurons, Pain, diabetes
Received: 25 Mar 2025; Accepted: 17 Jul 2025.
Copyright: © 2025 Mesa-Lombardo, García Magro, Nunez and Martin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yasmina B. Martin, Facultad de Medicina, Universidad Francisco de Vitoria, Pozuelo de Alarcón, Madrid, Spain
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.