Hearing loss affects synaptic balance in auditory cortex

听力损失会扰乱言语和语言习得，最终损害认知能力。 性能该提案的核心假设是，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电导之间的平衡，并严重限制了 初级听觉（Al）皮层神经元编码声学线索。耳聋将通过手术诱导， 听觉发作在沙鼠，和铝锥体神经元的性质将检查使用全细胞 记录技术在丘脑皮层脑切片制备。该研究计划将解决四个主要问题 问题：（1）听力损失是否影响铝的固有特性？A1神经元电活动的变化 特征将被检查，包括电紧张性和放电特性，以及向内和向外的关键 水流(2)听力损失是否影响铝兴奋性突触？丘脑诱发的兴奋性 将研究突触后电流（EPSC），包括其幅度和动力学。前或 突触后参与将通过激动剂的局灶性递送、mEPSC分析和EPSC评估。 失败率(3)听力损失是否影响铝抑制性突触？皮质内诱发的 将研究抑制性突触后电位（IPSPs），包括GABA a和GABA Ab的药理学 受体介导的成分。突触前或突触后受累将通过以下方法进行评估： GABA激动剂和微型IPSC。(4)听力损失会影响大脑皮层的处理吗？变化 将通过用矩形或正弦曲线串刺激丘脑传入神经来探索时间处理。 在记录Al中的EPSP的同时，将通过对皮层内的EPSP进行计时来评估突触整合。 电流或丘脑诱发的动作电位抑制。总之，这些结果对以下方面具有重要意义： 在细胞水平上了解听觉处理如何受到轻度到重度耳聋的影响，以及如何 我们可以弥补这些不足。

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.