Hearing loss affects synaptic balance in auditory cortex

描述（由申请人提供）：听力损失会干扰言语和语言习得，最终损害认知能力。该建议的核心假设是，感音神经性（SNHL）或传导性听力损失（CHL）破坏了兴奋性和抑制性传导之间的平衡，严重限制了初级听觉（Al）皮层神经元编码声音信号的能力。将在沙鼠听力发作前通过手术诱导耳聋，并在丘脑皮质脑切片制备中使用全细胞记录技术检查Al锥体神经元的特性。该研究计划将解决四个主要问题：(1)听力损失是否影响人工智能的内在特性？神经元电特性的变化将被检查，包括电紧张和放电特性，以及关键的内向和外向电流。(2)听力损失是否影响人工神经兴奋性突触？丘脑诱发的兴奋性突触后电流（EPSCs）的变化将被研究，包括它们的振幅和动力学。突触前或突触后受累将通过激动剂的局部递送、mEPSC分析和EPSC失败率来评估。(3)听力损失是否影响Al的抑制性突触？将研究皮质内诱发抑制性突触后电位（IPSPs）的变化，包括GABAa和GABAb受体介导成分的药理学。将通过局部递送GABA激动剂和微型IPSCs来评估突触前或突触后的受损伤。(4)听力损失是否影响皮质加工？在记录脑内epsp的同时，用矩形或正弦电流脉冲序列刺激丘脑传入事件，将探索颞叶加工的变化。突触整合将通过用电流或丘脑诱发的动作电位定时皮质内抑制来评估。总之，这些结果对于在细胞水平上理解听觉处理如何受到轻度到重度耳聋的影响，以及我们如何弥补这些缺陷具有重要意义。

DESCRIPTION (provided by applicant): Hearing loss can perturb speech and language acquisition and ultimately compromise cognitive performance. The core hypothesis of this proposal is that sensorineural (SNHL) or conductive hearing loss (CHL) disrupts the balance between excitatory and inhibitory conductances, and severely limits the ability of primary auditory (Al) cortex neurons to encode acoustic cues. Deafness will be surgically induced before hearing onset in gerbils, and the properties of Al pyramidal neurons will be examined using whole-cell recording techniques in a thalamocortical brain slice preparation. The research plan will address four major issues: (1) Does hearing loss influence intrinsic properties in Al? Changes in Al neuron electrical characteristics will be examined, including electrotonic and firing properties, and key inward and outward currents. (2) Does hearing loss influence excitatory synapses in Al? Changes in thalamus-evoked excitatory postsynaptic currents (EPSCs) will be investigated, including their amplitude and kinetics. Pre-or postsynaptic involvement will be assessed with focal delivery of agonists, mEPSC analyses, and EPSC failure rates. (3) Does hearing loss influence inhibitory synapses in Al? Changes in intracortically evoked inhibitory postsynaptic potentials (IPSPs) will be studied, including the pharmacology of GABAa and GABAb receptor mediated components. Pre-or postsynaptic involvement will be assessed with focal delivery of GABA agonists, and miniature IPSCs. (4) Does hearing loss affect cortical processing? Changes in temporal processing will be explored by stimulating thalamic afferents with trains of rectangular or sinusoidal current pulses while recording EPSPs in Al. Synaptic integration will be assessed by timing intracortical inhibition with current- or thalamus- evoked action potentials. Together, the results are significant for understanding at a cellular level how auditory processing is influenced by mild to severe deafness, and how we might compensate for these deficits.