Dynamic Regulation of Tuning in Adult Auditory Cortex

描述（由申请人提供）：本研究项目的目的是确定初级听觉皮层（Al）在听觉联想记忆（AAM）中的参与程度，并确定AAM的机制。与人工智能是静态声学处理器的传统观点相反，过去十年的研究已经确定，学习可以改变信息处理，特别强调行为获得性重要刺激的频率。值得注意的是，神经元的调谐会转向信号强化的音调频率。这种可塑性，就像记忆一样，是联想性的、高度特异性的、快速获得的、无限期保留的，并随着时间的推移而巩固。这些调谐转移增加了代表行为重要频率的皮层区域。因此，听觉皮层可能使用一种记忆代码，通过增加对刺激的细胞数量来暗示行为的重要性。我们将通过在简单和复杂的声学任务中对各组大鼠进行不同的训练来评估这一假设，以便通过正确表现的水平来确定音调获得不同程度的行为重要性。随后的人工智能映射将确定频率表示区域、其他细胞响应特性和学习到的刺激重要性之间的关系。基底核（NB）及其向听觉皮层的胆碱能（ACh）投射与学习诱导可塑性的机制有着深刻的联系，因为将音调与基底核刺激配对产生相同类型的可塑性，行为训练和阿托品应用于皮层会阻止可塑性。我们实验室最近的工作表明，将音调与新脑区的刺激配对，实际上会诱发预期的行为AAM。因此，我们将在简单和复杂的任务中充分表征nb诱导的AAM，包括其促进新辨别学习的能力，并确定其相关的Al可塑性。我们还将从这两种方法中比较人工智能的可塑性，以寻求初级听觉皮层中行为听觉联想记忆与表征可塑性之间的一般规律。这一发现将阐明大脑皮层的记忆功能，并为治疗提供基础，包括在遭受侮辱后恢复高级听觉功能和使用人工耳蜗学习感知语言。

DESCRIPTION (provided by applicant): The goal of this research project is to determine the involvement of the primary auditory cortex (Al) in auditory associative memory (AAM) and to identify the mechanisms of AAM. In contrast to traditional views that Al is a static acoustic processor, research during the past decade has established that learning modifies information processing to specifically emphasize the frequency of a behaviorally acquired important stimulus. Notably, neuronal tuning shifts toward/to the frequency of a tone that signals reinforcement. This plasticity, like memory, is associative, highly specific, rapidly acquired, retained indefinitely and consolidates over time. These tuning shifts increase the cortical area that represents behaviorally important frequencies. Thus, the auditory cortex may use a memory code that connotes behavioral importance by increasing the number of cells tuned to that stimulus. We will evaluate this hypothesis by differentially training groups of rats in simple and complex acoustic tasks, so that a tone gains different levels of behavioral importance, as indexed by levels of correct performance. Subsequent mapping of Al will determine the relationship between the area of frequency representation, other cellular response properties, and learned stimulus importance. The nucleus basalis (NB) and its cholinergic (ACh) projections to the auditory cortex have been deeply implicated as mechanisms of learning-induced plasticity because pairing a tone with NB stimulation produces the same types of plasticity as does behavioral training and atropine applied to the cortex blocks the plasticity. Recent work from our laboratory has revealed that pairing a tone with stimulation of the NB actually induces predicted behavioral AAM. Therefore, we will fully characterize NB-induced AAM in simple and complex tasks, including its ability to facilitate new discrimination learning, and determine its correlated Al plasticity. We will also compare Al plasticity from these two approaches to seek general rules relating behavioral auditory associative memory to representational plasticity in primary auditory cortex. The findings will elucidate cortical mnemonic function and provide a foundation for therapeutic treatments, including recovery of higher auditory function following insult and learning to perceive speech using cochlear implants.