The Effects of Developmental Hearing Loss on Inhibitory Short-term Plasticity

描述(由申请人提供)：在发育过程中遭受听力损失的人类可能会经历永久性的声音和语言感知障碍！这些损伤包括光谱时间处理的缺陷。听觉皮质中的抑制电路很容易受到听力损失的影响，可能是频谱处理的关键。具体地说，抑制传递表现出短期的可塑性，这可能有助于声刺激的时间模式的编码。我的初步数据表明，耳聋会改变抑制的短期可塑性。这项应用的目的是研究耳聋如何影响抑制性短期可塑性的正常发展，以及这些变化如何改变听觉皮质放电模式的有效性和时序。在听觉皮质神经元中进行的一系列全细胞实验被专门设计来表征(1)抑制性短期可塑性的正常发展(2)耳聋对抑制性短期可塑性的影响(3)抑制性短期可塑性对放电特性的影响。为了描述正常动物和耳聋动物抑制性短期可塑性的发展，将使用成对和多脉冲刺激来诱发一连串的抑制性突触事件。药物操作，特别是针对突触前和突触后的GABAB受体，将被用来揭示正常发育短期可塑性和耳聋后变化的机制。最后，为了了解这些变化的功能后果，我们将通过将突触抑制与神经元放电相结合来评估抑制性短期可塑性对脉冲效应和时间的影响。相关性：这些实验将评估抑制性突触时间反应的变化是否可以部分解释听力损失后的听觉处理缺陷，包括言语产生和感知方面的障碍。尤其是由于对GABAB受体药理学的广泛了解，揭示这些受体在时间反应中的参与将拓宽我们预防和减轻与听力损失相关的行为障碍的策略。

DESCRIPTION (provided by applicant): Humans who have suffered from periods of hearing loss during development can experience permanent debilitating impairments in sound and language perception! These impairments include deficits in spectrotemporal processing. Inhibitory circuits in the auditory cortex are vulnerable to hearing loss and may be critical for spectrotemporal processing. Specifically, inhibitory transmission displays short-term plasticity which may contribute to the encoding of temporal patterns of acoustic stimuli. My preliminary data suggests that inhibitory short-term plasticity is altered by deafness. The objective of this application is to study how deafness may impact normal development of inhibitory short-term plasticity and how these changes may alter efficacy and timing of auditory cortex discharge patterns. A series of whole-cell experiments in neurons of the'auditory cortex are specifically designed to characterize (1) the normal development of inhibitory short-term plasticity (2) the impact of deafness on inhibitory short- term plasticity (3) the effects of inhibitory short-term plasticity on discharge properties. To characterize development of inhibitory short-term plasticity in normal and deaf animals, paired and multiple-pulse stimuli will be used to evoke trains of inhibitory synaptic events. Pharmacological manipulations, particularly targeting pre and postsynaptic GABAB receptors, will be used to uncover the mechanisms underlying normal developmental short-term plasticity and the changes following deafness. Finally, to understand the functional consequences of these changes, the effects of inhibitory short-term plasticity on spike efficacy and timing will be evaluated by integrating synaptic inhibition with neuronal spiking. Relevance: These experiments will assess whether changes in temporal responses of inhibitory synapses may partially explain auditory processing deficits following hearing loss, including impairments in speech production and perception. Particularly due to pur extensive knowledge of GABAB receptor pharmacology, revealing the involvement of these receptors in temporal responses will broaden our strategies to prevent and alleviate behavioral deficits associated with hearing loss.