前庭代偿中毒蕈碱受体亚型差异性调节前庭小脑径路上前庭内侧核神经元兴奋性与突触传入的动态研究

Medial vestibular nucleus that project to cerebellum (CPMVNs) play a vital role in synaptic signal transmission of vestibulocerebellum. Muscarinic receptor (mAChRs) M2 and M3 subtypes are previously determined to differentially control synaptic input and excitability of CPMVNs; the metabotropic glutamate receptor expression and spontaneous firing frequency of CPMVNs in both contralateral and operation side altered dynamically at different point-in-time after unilateral labyrinthectomy. Accordingly the function of mAChRs subtypes that differentially control synaptic input and excitability of CPMVNs are assumed to have dynamic change in process of vestibular compensation. In this project, we plan to detect the following three areas in animal model of vestibular compensation: 1. Expression of relevant mAChRs subtypes in MVN； 2. Modulation effect of mAChRs on excitatory presynaptic glutamate input and inhibitory postsynaptic GABA input of CPMVNs; 3. Spontaneous firing characteristic and cholinergic excitability of CPMVNs. This research helps to reveal the intrinsic properties of plasticity changes in synapsis and neurons of vestibulocerebellum pathway in vestibular compensation, and has important therapeutic implications for treating vestibular disorders.

投射至小脑的前庭内侧核神经元（CPMVNs）是前庭小脑通路突触信号传递接收的主要载体。前期研究发现毒蕈碱受体（mAChRs）兴奋性突触后M3亚型与抑制性突触前M2亚型差异性调节CPMVNs自发性放电活动及其突触前谷氨酸能传入，在单侧迷路切除术（UL）后不同时程，术侧、对侧MVN区代谢性谷氨酸受体表达及CPMVNs自发性放电频率存在动态改变，据此推测前庭代偿中mAChRs 亚型差异性调节CPMVNs上突触传入及神经元胆碱能兴奋性存在动态变化。本课题拟检测前庭代偿过程中：1. MVN上mAChRs亚型表达; 2. mAChRs对CPMVNs兴奋性突触前谷氨酸能传入和抑制性突触后GABA能传入调制作用; 3. CPMVNs自发性放电特性及胆碱能兴奋性作用。以上研究将有助于进一步明确前庭代偿过程中前庭小脑通路上突触及神经元可塑性变化的本质，为前庭代偿机制研究及眩晕的治疗提供必要的电生理依据。

投射至小脑的前庭内侧核神经元（CPMVNs）是前庭小脑通路突触信号传递接收的主要载体。前期研究发现毒蕈碱受体（mAChRs）兴奋性突触后M3亚型与抑制性突触前M2亚型差异性调节CPMVNs自发性放电活动及其突触前谷氨酸能传入，在单侧迷路切除术后不同时程，术侧、对侧MVN区代谢性谷氨酸受体表达及CPMVNs自发性放电频率存在动态改变，据此推测前庭代偿中mAChRs差异性调节CPMVNs上突触传入及神经元胆碱能兴奋性存在动态变化。本课题检测前庭代偿过程中：1. MVN相应mAChRs、谷氨酸受体表达。2. mAChRs对CPMVNs兴奋性突触前谷氨酸能传入和抑制性突触后GABA能传入调制作用。3. CPMVNs自发性放电特性及胆碱能兴奋性作用。以上研究将有助于进一步明确前庭代偿过程中前庭小脑通路上突触及神经元可塑性变化的本质，为前庭代偿机制研究及眩晕的治疗提供必要的电生理学依据。