A Multidisciplinary Approach to Simultaneously Monitoring Real-Time Neuronal Activity and Pain Behaviors During Optogenetic Stimulation of Brain Neurons in Freely Moving Mice.
A Multidisciplinary Approach to Simultaneously Monitoring Real-Time Neuronal Activity and Pain Behaviors During Optogenetic Stimulation of Brain Neurons in Freely Moving Mice.
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DOI：
10.2147/jpr.s334256
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发表时间：
2021
影响因子：
2.7
通讯作者：
Tao F
中科院分区：
文献类型：
--
作者：
Crawford J;Liu S;Tao F
当前阿片类药物流行突出表明，确定治疗慢性三叉神经痛的新疗法是一项关键需求。为了开发这些治疗方法，有必要在大脑中有可行的靶点。从历史上看，神经追踪研究在确定大脑区域之间的连接方面非常有用，但不能提供有关这些连接功能的信息。结合光遗传学和行为观察，研究人员可以确定特定的大脑区域是否参与了这种行为的调节。多通道电生理记录的增加提供了关于特定神经元通路中的实时神经元活动的信息。雄性C57/BL/6 J小鼠（8周龄）接受眶下神经慢性压迫性损伤（CCI-ION）或假手术，并在下丘脑A11核中注射通道视紫红质（ChR 2）或对照病毒。CCI-ION后两周，他们在实时位置偏好（RTPP）进行测试，同时记录三叉神经脊束核尾侧（Sp 5C）的神经元活动。A11神经元的光致兴奋导致在RTPP测试期间在刺激室中花费更多时间。此外，与注射对照病毒或经历假手术的动物相比，A11的刺激导致注射携带ChR 2的AAV的动物中Sp 5C中更大数量的神经元活性增加。体内多通道电生理记录、光遗传学刺激和行为观察可以在慢性三叉神经性疼痛的小鼠模型中组合以验证参与这种疼痛的调节的脑区域。
Highlighted by the current opioid epidemic, identifying novel therapies to treat chronic trigeminal neuropathic pain is a critical need. To develop these treatments, it is necessary to have viable targets in the brain to act on. Historically, neural tracing studies have been extremely useful in determining connections between brain areas but do not provide information about the functionality of these connections. Combining optogenetics and behavioral observation allows researchers to determine whether a particular brain area is involved in the regulation of such behavior. The addition of multi-channel electrophysiological recording provides information on real-time neuronal activity in the specific neuronal pathway. Male C57/BL/6J mice (8-week-old) underwent either chronic constriction injury of infraorbital nerve (CCI-ION) or a sham surgery and were injected with either channelrhodopsin (ChR2) or a control virus in the hypothalamic A11 nucleus. Two weeks after CCI-ION, they were tested in real-time place preference (RTPP), while neuronal activity in the spinal trigeminal nucleus caudalis (Sp5C) was recorded. Optogenetic excitation of the A11 neurons results in more time spent in the stimulation chamber during RTPP testing. Additionally, stimulation of the A11 results in a greater number of neuronal activity increase in the Sp5C in animals with the injection of AAV carrying ChR2 compared to animals injected with a control virus or that underwent a sham surgery. In vivo multi-channel electrophysiological recording, optogenetic stimulation, and behavioral observation can be combined in a mouse model of chronic trigeminal neuropathic pain to validate brain areas involved in the modulation of such pain.