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Shanghai University of Traditional Chinese Medicine

Ministry of Education (Shanghai University of Traditional Chinese Medicine)

Cortical spreading depression (CSD) is an electrophysiological event underlying migraine aura. Traditional CSD models are invasive and often cause injuries. The aim of the study was to establish a minimally invasive optogenetic CSD model and identify the active networks after CSD using whole-brain activity mapping.

Cortical pain induced by optogenetic cortical spreading depression: from whole brain activity mapping.

Migraine, a complex brain disorder, is regarded as a possible clinical manifestation of brain energy dysfunction. The trigeminovascular system is considered the basis for the pathogenesis of migraine, hence we depicted the proteomics profiling of key regions in this system, then focusing on protein alterations related to mitochondrial function. The aim of this study is to illustrate the role of mitochondria in migraine.

Proteomics profiling reveals mitochondrial damage in the thalamus in a mouse model of chronic migraine.

Both epidemiological and clinical studies have indicated that headache and sleep disturbances share a complex relationship. Although headache and sleep share common neurophysiological and anatomical foundations, the mechanism underlying their interaction remains poorly understood. The structures of the diencephalon and brainstem, particularly the locus coeruleus (LC), are the primary sites where the sleep and headache pathways intersect. To better understand the intricate nature of the relationship between headache and sleep, our study focused on investigating the role and function of noradrenergic neurons in the LC during acute headache and acute sleep disturbance.

The crucial role of locus coeruleus noradrenergic neurons in the interaction between acute sleep disturbance and headache.

Migraine is the second disabling neurological disorder with a high prevalence. Aura occurs in one-third of migraineurs and visual aura accounts for over 90%. Cortical spreading depression (CSD) underlies aura and might trigger migraine headaches. Compared with CSD induction by invasive electrical, chemical, or mechanical stimulation, optogenetics avoids direct influences on meninges in the stimulation process. However, previous optogenetic CSD models mainly use Thy1-ChR2-YFP or CaMKIIα-cre transgenic mice. They are limited when the pathogenesis study requires transgenic mice to express other specific promotor, such as the dopamine or serotonin transporter promotor. In addition, reported behavioral paradigms were based on CSD induction under anesthesia. This study aimed to establish an optogenetic CSD-induced migraine model originating in the primary visual cortex (VISp) in C57BL/6 J mice and presented the behavioral paradigm when CSD induction was under awake condition.

Optogenetic cortical spreading depression originating from the primary visual cortex induces migraine-like pain and anxiety behaviors in freely moving C57BL/6 J mice.

ArticleTotal : 2	Year
Publication title	2026
Publication title	2026

Article	Year
Cortical pain induced by optogenetic cortical spreading depression: from whole brain activity mapping. Molecular brain\| PubMed ID: 36471383	2022
Proteomics profiling reveals mitochondrial damage in the thalamus in a mouse model of chronic migraine. The journal of headache and pain\| PubMed ID: 37667199	2023
The crucial role of locus coeruleus noradrenergic neurons in the interaction between acute sleep disturbance and headache. The journal of headache and pain\| PubMed ID: 38443795	2024
Optogenetic cortical spreading depression originating from the primary visual cortex induces migraine-like pain and anxiety behaviors in freely moving C57BL/6 J mice. The journal of headache and pain\| PubMed ID: 40011818	2025

Chunxiao Yang

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