Hearing loss affects synaptic balance in auditory cortex

描述(由申请人提供)：听力损失会扰乱言语和语言习得，最终影响认知能力。这一提议的核心假设是感觉神经性(SNHL)或传导性听力损失(CHL)破坏了兴奋性和抑制性电导之间的平衡，并严重限制了初级听觉(Al)皮质神经元编码声音提示的能力。将在沙土鼠听力发作之前通过手术诱导耳聋，并将在丘脑皮质脑片制备中使用全细胞记录技术检查铝锥体神经元的特性。这项研究计划将解决四个主要问题：(1)听力损失是否影响阿尔茨海默病的内在特性？将检查铝神经元电特性的变化，包括电紧张性和放电特性，以及关键的内向和外向电流。(2)听力损失是否影响铝的兴奋性突触？将研究丘脑诱发的兴奋性突触后电流(EPSCs)的变化，包括其幅度和动力学。突触前或突触后的参与将通过局部注射激动剂、mEPSC分析和EPSC失败率来评估。(3)听力损失是否影响铝内抑制性突触？将研究大脑皮质内诱发的抑制性突触后电位(IPSP)的变化，包括GABAA和GABAB受体介导成分的药理学。突触前或突触后的参与将通过GABA激动剂和微型IPSCs的焦点传递来评估。(4)听力损失是否影响皮质处理？时间处理的变化将通过用矩形或正弦电流脉冲序列刺激丘脑传入来探索，同时记录A1的EPSP。突触整合将通过电流或丘脑诱发的动作电位对皮质内抑制进行计时来评估。总而言之，这些结果对于在细胞水平上理解轻度到重度耳聋如何影响听觉处理，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.