Functions of Associative Auditory Cortical Plasticity

描述（由申请人提供）：听觉理解和听觉分析对听力至关重要。对声音的理解需要持久的听觉记忆，即，对声音的学习意义的存储。听觉记忆的丰富和复杂的领域是由听觉皮层的可塑性。例如，学习伴随着频率调谐的变化，以强调在行为上变得重要的声音，如在联想学习期间。虽然学习诱导的皮层可塑性的事实现在已经得到了很好的证实，但它本身既不能提供对听觉记忆的神经基础的充分理解，也不能将基础知识有效地应用于听觉和交流的临床问题。确定皮层可塑性的记忆功能是必要的。本研究项目的目标是确定学习诱导的皮层可塑性的记忆功能和胆碱能基底核作为介导这些功能的机制的作用。我们假设，联想听觉可塑性的三个主要功能是通过（1）使听觉记忆更强，（2）保留其声学细节和（3）促进其灵活使用以解决新的听觉问题来增强听觉记忆。为了确定塑性的功能，必须控制塑性。我们已经开发了两种控制可塑性的方法：（a）间接地通过指导学习策略，（B）直接地通过刺激基底核。为了验证这些假设，并揭示记忆功能的联想可塑性，我们将训练大鼠与微电极长期植入其初级听觉皮层（A1），酒吧按水的存在下的音调。我们将跟踪行为和可塑性的发展，并获得完整的功能地图A1在动物的一个子集，通过获得重复的配置文件的神经元放电和局部场电位响应范围广泛的纯音频率水平的组合。训练后测试将评估记忆强度、对声学体验细节的记忆以及与适当的对照组相比学习隐藏线索回避任务的能力。如果基底核（NB）可以冥想A1的记忆功能，那么将音调与NB刺激配对以诱导A1可塑性和听觉记忆，应该增加记忆强度水平，保留声学细节并促进回避学习。这些发现对治疗干预的设计和实施具有直接的翻译意义，包括儿童语音处理缺陷的补救和人工耳蜗植入后学习理解语音。矫正训练的最佳设计将直接受益于促进所需类型的特定皮层可塑性（通过头皮记录或功能成像评估），可以为每个患者定制设计，以促进强大，特定和灵活的听觉记忆。 公共卫生相关性：听觉理解和听觉分析对听力至关重要，因为它可以识别包括语音在内的所有声音。这个项目的结果将大大增加我们对大脑如何获取，代表，存储和利用听觉经验的理解。这些发现将直接关系到治疗干预措施的设计和实施，以实现和改善一般的听觉和言语理解。

DESCRIPTION (provided by applicant): Auditory comprehension, as well as auditory analysis, is essential for hearing. The comprehension of sound requires enduring auditory memory, i.e., the storage of the learned meanings of sounds. The rich and complex domain of auditory memory is enabled by the plasticity of the auditory cortex. For example, learning is accompanied by shifts of frequency tuning to emphasize sounds that become behaviorally important, as during associative learning. Although the fact of learning-induced cortical plasticity is now well-established, it alone cannot provide either an adequate understanding of the neural bases of auditory memory or the effective application of basic knowledge to clinical problems in hearing and communication. It is essential to determine the memory functions of cortical plasticity. The goals of this research project are to determine the memory functions of learning-induced cortical plasticity and the role of the cholinergic nucleus basalis as a mechanism mediating those functions. We hypothesize that three main functions of associative auditory plasticity are to enhance auditory memories by (1) making them stronger, (2) preserving their acoustic details and (3) promoting their flexible use to solve new auditory problems. To determine the functions of plasticity, it is necessary to control plasticity. We have already developed two ways to control plasticity: (a) indirectly by guiding learning strategies, (b) directly by stimulating the nucleus basalis. To test these hypotheses and reveal mnemonic functions of associative plasticity we will train rats with microelectrodes chronically implanted in their primary auditory cortex (A1), to bar-press for water in the presence of a tone. We will track the development of behavior and plasticity, and obtain complete functional maps of A1 in a subset of animals, by obtaining repeated profiles of neuronal discharge and local field potential responses to a broad range of pure tone frequency-level combinations. Post-training tests will assess memory strength, memory for details of acoustic experience and the ability to learn an auditory-cued avoidance task compared to appropriate control groups. If the nucleus basalis (NB) can meditate memory functions of A1, then pairing a tone with NB stimulation to induce A1 plasticity and auditory memory should increase the level of memory strength, retention of acoustic details and facilitate avoidance learning. The findings have direct translational implications for the design and implementation of therapeutic interventions, including remediation of phonological processing deficits in children and learning to comprehend speech following cochlear implantation. The optimal design of remediation training will directly benefit from promoting the desired type of specific cortical plasticity (assessed by scalp recordings or functional imaging) that can be custom-designed for each patient to promote strong, specific and flexible auditory memory. PUBLIC HEALTH RELEVANCE: Auditory comprehension, as well as auditory analysis, is essential for hearing as it enables the recognition of all sounds including speech. The results of this project will significantly increase our understanding of how the brain acquires, represents, stores and utilizes auditory experience. The findings will be directly relevant to the design and implementation of therapeutic interventions, to enable and improve general auditory and speech comprehension.