Inhibition of glutamatergic trigeminal nucleus caudalis- vestibular nucleus projection neurons attenuates vestibular dysfunction in the chronic-NTG model of migraine
Yun Zhang, Yixin Zhang, Yanyun Wang, Xiaoyan Zhang, Guangcheng Qin, Dunke Zhang, Lixue Chen, Jiying Zhou, Lixue Chen, Jiying Zhou
Abstract
BACKGROUND: Prior clinical studies suggest a shared mechanism between vestibular symptoms and migraine headache. However, the specific neuroanatomical substrate connecting vestibular symptoms with migraine remains to be largely unknown. Thus, the aim of this study was to further investigate the mechanisms that whether and how trigeminovestibular neurons produce effects on neuronal activation in vestibular nucleus (VN). METHODS: A chronic-NTG rat model was established by recurrent intermittent administration of nitroglycerin (NTG). Pain- and vestibular-related behaviors were assessed. To selectively inhibit the glutamatergic neurons and trigeminal nucleus caudalis (TNC) to VN projection neurons, the AAVs encoding engineered Gi-coupled hM4D receptor were administered in the TNC or VN area. RESULTS: neurons alleviates vestibular dysfunction in the chronic-NTG rat. Calcitonin gene-related peptide (CGRP)-expressing neurons in the VN received glutamatergic projections from TNC neurons. Silencing the glutamatergic TNC-VN projection neurons attenuates vestibular dysfunction in the chronic-NTG rat. CONCLUSIONS: Together, we reveal a modulatory role of glutamatergic TNC-VN projection neurons in vestibular dysfunction of migraine.