Activation of the VpdmVGLUT1-VPM pathway contributes to anxiety-like behaviors induced by malocclusion

Yuan-Yuan Ji; Xin Liu; Xin Li; Yi-Fan Xiao; Teng Ma; Jian Wang; Yue Feng; Juan Shi; Mei-Qing Wang; Jin-Lian Li; Jiang-Hua Lai

doi:10.3389/fncel.2022.995345

Activation of the Vpdm^VGLUT1-VPM pathway contributes to anxiety-like behaviors induced by malocclusion

Front Cell Neurosci. 2022 Dec 20:16:995345. doi: 10.3389/fncel.2022.995345. eCollection 2022.

Authors

Yuan-Yuan Ji^{1

2

3}, Xin Liu^{4

5}, Xin Li⁵, Yi-Fan Xiao², Teng Ma⁶, Jian Wang⁷, Yue Feng¹, Juan Shi³, Mei-Qing Wang⁴, Jin-Lian Li^{2

3}, Jiang-Hua Lai¹

Affiliations

¹ College of Forensic Science, Xi'an Jiaotong University, Xi'an, China.
² Department of Anatomy, School of Medicine, Northwest University, Xi'an, China.
³ Department of Anatomy, K. K. Leung Brain Research Centre, Fourth Military Medical University, Xi'an, China.
⁴ State Key Laboratory of Military Stomatology, Department of Oral Anatomy and Physiology, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, School of Stomatology, Fourth Military Medical University, Xi'an, China.
⁵ Department of Stomatology, The 960th Hospital of People's Liberation Army, Jinan, China.
⁶ Functional and Molecular Imaging Key Lab of Shaanxi Province, Department of Radiology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
⁷ Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.

Abstract

Occlusal disharmony has a negative impact on emotion. The mesencephalic trigeminal nucleus (Vme) neurons are the primary afferent nuclei that convey proprioceptive information from proprioceptors and low-threshold mechanoreceptors in the periodontal ligament and jaw muscles in the cranio-oro-facial regions. The dorsomedial part of the principal sensory trigeminal nucleus (Vpdm) and the ventral posteromedial nucleus (VPM) of thalamus have been proven to be crucial relay stations in ascending pathway of proprioception. The VPM sends numerous projections to primary somatosensory areas (SI), which modulate emotion processing. The present study aimed to demonstrate the ascending trigeminal-thalamic-cortex pathway which would mediate malocclusion-induced negative emotion. Unilateral anterior crossbite (UAC) model created by disturbing the dental occlusion was applied. Tract-tracing techniques were used to identify the existence of Vme-Vpdm-VPM pathway and Vpdm-VPM-SI pathway. Chemogenetic and optogenetic methods were taken to modulate the activation of Vpdm^VGLUT1 neurons and the Vpdm-VPM pathway. Morphological evidence indicated the involvement of the Vme-Vpdm-VPM pathway, Vpdm-VPM-SI pathway and Vpdm^VGLUT1-VPM pathway in orofacial proprioception in wild-type mice and vesicular glutamate transporter 1 (^VGLUT1): tdTomato mice, respectively. Furthermore, chemogenetic inhibition of Vpdm^VGLUT1 neurons and the Vpdm-VPM pathway alleviated anxiety-like behaviors in a unilateral anterior crossbite (UAC) model, whereas chemogenetic activation induced anxiety-like behaviors in controls and did not aggravate these behaviors in UAC mice. Finally, optogenetic inhibition of the Vpdm^VGLUT1-VPM pathway in VGLUT1-IRES-Cre mice reversed UAC-induced anxiety comorbidity. In conclusion, these results suggest that the Vpdm^VGLUT1-VPM neural pathway participates in the modulation of malocclusion-induced anxiety comorbidity. These findings provide new insights into the links between occlusion and emotion and deepen our understanding of the impact of occlusal disharmony on brain dysfunction.

Keywords: anxiety; principal sensory trigeminal nucleus; temporomandibular disorder; unilateral anterior crossbite; ventral posteromedial nucleus of thalamus; vesicular glutamate transporter 1.