Functions of Associative Auditory Cortical Plasticity

描述(申请人提供)：听觉理解和听觉分析对听力是必不可少的。对声音的理解需要持久的听觉记忆，即存储已学习的声音意义。听觉记忆丰富而复杂的领域是由听觉皮质的可塑性实现的。例如，学习伴随着频率调谐的变化，以强调行为上重要的声音，就像在联想学习中一样。尽管学习诱导皮质可塑性的事实现在已经得到了充分的证实，但仅凭这一事实既不能充分理解听觉记忆的神经基础，也不能有效地应用基本知识来解决听力和沟通方面的临床问题。确定大脑皮质可塑性的记忆功能是必要的。本研究项目的目的是确定学习诱导的皮质可塑性的记忆功能，以及胆碱能基底核作为调节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)增强听觉记忆，(2)保留其听觉细节，(3)促进它们的灵活使用来解决新的听觉问题。要确定塑性的功能，就必须控制塑性。我们已经开发出两种方法来控制可塑性：(A)间接地通过指导学习策略来控制可塑性；(B)通过直接刺激基底核来控制可塑性。为了测试这些假说并揭示联想可塑性的助记功能，我们将用长期植入大鼠初级听觉皮质(A1)的微电极来训练大鼠，让它们在有声音的情况下按压水。我们将跟踪行为和可塑性的发展，并通过获得神经元放电和对广泛的纯音频率水平组合的局部场电位响应的重复轮廓，获得A1在动物子集中的完整功能图。训练后的测试将评估记忆强度、对声音体验细节的记忆，以及与适当的控制组相比学习听觉提示的回避任务的能力。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会增加记忆强度，保持声音细节，并促进回避学习。这些发现对设计和实施治疗干预措施具有直接的翻译意义，包括修复儿童的语音处理缺陷和学习理解人工耳蜗植入后的言语。治疗训练的最佳设计将直接受益于促进所需类型的特定皮质可塑性(通过头皮记录或功能成像进行评估)，这种可塑性可以为每个患者定制，以促进强大、特定和灵活的听觉记忆。 与公共卫生相关：听觉理解和听觉分析对听力至关重要，因为它能够识别包括语音在内的所有声音。这个项目的结果将显著增加我们对大脑如何获取、表示、存储和利用听觉经验的理解。这些发现将与设计和实施治疗干预措施直接相关，以支持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.