谷氨酸-GABA稳态与海马对前庭神经核的平衡调控作用的生物学机制研究

Vertigo is a common clinical disorder of otology, which serious impact quality of life. Vestibular compensation is a complex change of central plasticity process, and the mechanisms are complicated. The present studies were limited to the vestibular nucleus and the cerebellum, the research of higher level center was apparently rare. Researches have shown that hippocampal place cells could respond to vestibular stimulation, and vestibular stimulation could also affect some neurotransmitters and neuronal cell proliferation in the hippocampus. We speculate that the hippocampus may play an important role in the vestibular compensation. In this research, based on the unilateral labyrinthectomy animal model of vertigo，we observe the effect of hippocampal damage on the behavior change of animals in the process of vestibular compensation, and record changes of neuronal cells firing rate , neurotransmitters such as glutamate, GABA, magnesium ion, ascorbic acid and energy substance of the vestibular nucleus complex with in vivo electrophysiological and microdialysis methods in conscious animals. We attempt to reveal the molecular and electrophysiological mechanism between vestibular nucleus complex and hippocampus，and to explore the action mechanism of the hippocampus during vestibular compensation. We apply the nerve nucleus stereotactic technique, microdialysis sampling in vivo, chronic dynamic electrophysiological technique and electrochemical detection, to the study of vestibular compensation pathogenesis. This research will be of significance importance not only in the mechanism but also in the treatment of vestibular compensation.

眩晕是耳科常见的临床症状之一，严重影响患者的生活质量。前庭代偿发生机制复杂，目前研究均局限于前庭神经核与小脑，缺乏对更高级中枢的研究。最新研究结果表明前庭刺激可以引起海马神经元电信号、神经递质、细胞增殖及生理功能的改变。由此推测海马在前庭代偿中也可能起到了重要作用。本项目拟通过单侧迷路切除的方式建立眩晕动物模型，通过动物行为学的方式观察损毁海马对前庭代偿的影响，并且通过清醒活体微透析和慢性电生理的方式，观察损毁海马对前庭神经核神经元放电，谷氨酸、GABA等神经递质，镁离子、抗坏血酸及能量物质的变化规律，试图揭示海马在前庭代偿中对前庭神经核的可能调控机制。本研究将脑神经核团立体定位技术、微透析技术活体取样、慢性动态电生理技术和电化学检测巧妙、有机地应用于前庭代偿的神经生理学发病机制研究中，为揭示前庭代偿的病理生理机制做探索性的基础工作，为前庭代偿的治疗提供理论依据和策略。

研究内容：探究前庭内侧核及海马在眩晕发病机制中的作用。.重要的结果：海马脑区细胞外液的抗坏血酸的基础水平为27 ± 14 μM，冰水刺激外耳道诱发眩晕过程中，其抗坏血酸浓度水平则下降至其基础水平的55% ± 12%；而对照组（耳廓冰水及耳道温水刺激）抗坏血酸水平无明显变化；此外，海马神经元的基础自发放电率为14.1 ± 3.0 spikes/s，其神经元自发放电率在冰水刺激后立刻下降，约 1小时恢复至正常水平。.前庭内侧核细胞外液抗坏血酸基础水平为29 ± 17 μM，冰水刺激外耳道时诱发眩晕时，其抗坏血酸浓度升高至其基础水平的155% ± 14%，；而对照组（耳廓冰水及耳道温水刺激）抗坏血酸水平无明显变化；此外，前庭内侧核神经元的基础自发放电率为21.3 ± 4.6 spikes/s，在冰水刺激时其神经元自发放电率升高，约1小时恢复正常水平。.科学意义：外周性眩晕是由于前庭通路上一侧传入信号障碍导致的。前庭神经核是前庭传导通路上的第二级神经元，是外周前庭通路与前庭中枢相连接的关键核团；前庭代偿是涉及多个大脑区域如海马等的中枢可塑性变化过程，成功的前庭代偿对眩晕的发生起着重要的作用。.我们的研究发现眩晕疾病模型中海马脑区神经电活动及神经调质抗坏血酸的变化规律，为海马在前庭代偿中所起的作用提供实验依据，为前庭代偿的治疗提供一些新的药物作用的靶点。