Dynamic Regulation of Tuning in Adult Auditory Cortex

描述(申请人提供)：本研究计划的总体长期目标是了解初级听觉皮质(A1)在听觉联想记忆(AAM)中的参与，并确定AAM的机制。与传统的认为A1是严格意义上的声学分析器的观点不同，当代的研究证实，学习以高度特定的方式修改了声学信息的处理、表示和存储，以强调行为上重要的声音。实验的具体目的是确定(1)控制特定皮质可塑性的类型、程度和保持的因素，包括学习策略、训练量和声刺激的类型，(2)训练过程中可塑性发展的本质及其长期保持，以及(3)声音与胆碱能基底核(NB)激活所诱导的听觉联想记忆的属性。大鼠将接受各种基于听觉的任务的训练，这些任务包括在学习的不同阶段详细记录A1的神经元放电，或在完成学习任务后对A1进行全面的映射。为了验证胆碱能系统激活参与正常听觉记忆诱导的假设，我们将确定NB诱导的记忆是否也能够长期保持、辨别和转移到新的情境。这些发现将阐明皮质助记功能，并为治疗治疗提供基础，包括侮辱后高级听觉功能的经验依赖恢复，以及人工耳蜗植入治疗后学习感知语音。这些发现将显著增加我们对听觉皮质功能的一个基本方面的理解，即基于经验的神经可塑性。因此，它们将与声音特征如何与经验相互作用以产生听觉理解的核心问题，以及听觉系统损伤的治疗和学习通过人工耳蜗植入等假体手段理解语言的核心问题高度相关。

DESCRIPTION (provided by applicant): The overall long-term objective of this research program is to understand the involvement of the primary auditory cortex (A1) in auditory associative memory (AAM) and to identify mechanisms of AAM. In contrast to traditional views that A1 is strictly an acoustic analyzer, contemporary research has established that learning modifies the processing, representation and storage of acoustic information in highly-specific ways, to emphasize behaviorally important sounds. The specific aims of the experiments are to determine (1) the factors that govern the type, degree and retention of specific cortical plasticity, including learning strategy, amount of training and type of acoustic stimulus, (2) the nature of the development of plasticity during training and its long term-retention and (3) the attributes of auditory associative memory that is induced by sound paired with activation of the cholinergic nucleus basalis (NB). Rats will be trained in a variety of acoustically-based tasks involving detailed recording of neuronal discharges in A1 either during various stages of learning or comprehensive mapping of A1 after the completion of learning tasks. To test the hypothesis that activation of the cholinergic system is involved in the induction of normal auditory memory, we will determine if NB- induced memory also is capable of long-term retention, discrimination, and transfer to new situations. The findings will elucidate cortical mnemonic function and provide a foundation for therapeutic treatments including experience-dependent recovery of higher auditory function following insult, and learning to perceive speech following cochlear implant treatments. These findings will significantly increase our understanding of a fundamental aspect of auditory cortical function, that of experience-based neural plasticity. Therefore, they will be highly relevant both to the central issue of how features of sound interact with experience to produce auditory comprehension, and for therapeutic treatments of auditory system impairment and learning to understand speech via prosthetic means such as cochlear implants.