优先效应中上橄榄外侧核与外侧丘系背核对下丘的抑制性调控

The poor ability of sound localization leads to lower speech perception scores of patients received hearing aids. In a reverberant environment，the precedence effect(PE) is the ability to localize the original sound correctly without disturbed by the reflected sound, which is thought to be responsible for the ability to localize and perceive sounds accurately and for accurate speech perception. Although the psychoacoustics associated with precedence effect has been well described, the underlying neural mechanisms, especially the neural circuits responsible for mediating the suppressive effects, are poorly understood. The inferior colliculus(IC) occupies a critical relay station in both ascending and descending auditory pathways, and is widely examined in studies on physiological correlates of PE. The object of this project is to study the inhibiting mechanisms of PE between IC and lateral superior olivary(LSO),dorsal nucleus of the lateral lemniscus(DNLL).Experiments will be conducted in IC of SD rats using extracellular recordings in vivo and whole-cell patch clamp recordings of slices of IC in vitro. In vivo and vitro studies，the responses of neurons in IC will be elicited by sound and electric stimulis simulateing PE in a natural situation.The inhibiting neurotransmitter antagonists will be ejected to neurons of IC.Furthemore,HRP retrograde tracing from the PE neurons in IC to LSO and DNLL, electrolytic lesions of LSO and DNLL，and immunohistochemisty will be performed. By those studies, the types of the neurotransmitters and neural circuits between IC and LSO, DNLL will be confirmed，which may participate in PE. Finally, the underlying neural inhibiting modulation of LSO and DNLL on IC in PE may be speculated, which would be help to understand the neural mechanisms of echo suppression.

声源定位能力是影响辅听患者言语识别率的重要因素之一。优先效应是听者在复杂声环境中定位声源的基础，它的存在使听者可不受回声干扰而准确定位原始声源。本项目主要研究优先效应中上橄榄外侧核（LSO）与外侧丘系背核（DNLL）对下丘的抑制性调控作用，进而为阐明复杂声环境下声源定位和言语识别机制提供线索。本项目主要采用电生理技术结合分子生物技术，给予大鼠模拟优先效应的声刺激和电刺激，在体细胞外记录及离体膜片钳记录大鼠下丘优先效应神经元电活动；微电泳递质拮抗剂及神经束路追踪加免疫组化双标法，研究确定参与LSO与DNLL调控下丘优先效应神经元的递质类型和神经通路；并通过核团毁损进一步验证这两个核团对下丘的抑制性调控在听觉优先效应中的作用。通过此研究，可明确优先效应中LSO与DNLL对下丘抑制性调控作用机制，为寻找有效方法提高辅听患者的声源定位和言语识别能力奠定理论基础。

声源定位能力是影响人工辅听患者言语识别率的重要因素之一，优先效应是保证听者在复杂声环境下准确定位原始声源并进行正确言语识别的重要因素。以下丘为中心、抑制性投射为主的神经调节网络被认为与优先效应的产生有关，但该点目前尚缺乏直接实验证据支持。本项目主要应用电生理技术，从在体和离体两方面分别阐述上述问题。在体部分：通过在体细胞外记录技术，比较在标准优先效应刺激声环境中，下丘神经元在局部微电泳抑制性神经递质前后放电反应变化。离体部分：通过离体膜片钳技术，观察下丘神经元突触后电流及连续放电反应受电刺激外侧丘系背核的影响。通过实验发现：①下丘局部微量注射γ-氨基丁酸后，神经元放电幅值降低，半极大刺激时间间隔延长（F=215.15，P=0.000<0.05），对滞后声平均标准化反应恢复曲线右移（Fbetween-subject=339.78，P=0.000<0.05），说明γ-氨基丁酸可增强下丘神经元对滞后声反应的压制。②下丘不同时间发放类型神经元的优先效应表现不同，表现为相同刺激时间间隔下紧张发放型神经元的滞后声反应较相位发放型神经元强，且随着刺激时间间隔延长，前者对滞后声的反应的恢复较后者更快(Fbetween-subject =27.92, P=0.000<0.05)。③电刺激外侧丘系背核，在下丘神经元记录到抑制性突触后电流，加入荷包牡丹碱后该电流消失。④电刺激外侧丘系背核，两种放电类型神经元均表现为适应比增大。其中两种各有一神经元表现为受电刺激外侧丘系背核的压制，加入荷包牡丹碱后，持续规律放电型恢复至规律放电，而持续适应型放电间期较前延长，适应比增大。在两种神经元中均未发现长时程抑制现象。通过该研究，探究了外侧丘系背核对下丘抑制性调控的机制，为进一步揭示听觉优先效应的神经生理机制提供了实验依据。