Functions of Associative Auditory Cortical Plasticity

描述（由申请人提供）：听觉理解和听觉分析对于听力是必不可少的。对声音的理解需要持久的听觉记忆，即对所学到的声音意义的存储。听觉皮层的可塑性使听觉记忆的丰富和复杂领域得以实现。例如，在联想学习过程中，学习伴随着频率调整的变化，以强调那些在行为上变得重要的声音。虽然学习诱发的皮质可塑性这一事实现已得到证实，但仅凭这一事实既不能充分理解听觉记忆的神经基础，也不能有效地将基础知识应用于听力和交流的临床问题。确定大脑皮层可塑性的记忆功能是至关重要的。本研究的目的是确定学习皮质可塑性的记忆功能以及胆碱能基底核在这些功能中的作用。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)保留听觉细节，(3)促进听觉记忆的灵活使用来解决新的听觉问题。要确定塑性的作用，就必须对塑性进行控制。我们已经开发了两种控制可塑性的方法：(a)间接通过指导学习策略，(b)直接通过刺激基底核。为了验证这些假设并揭示联想可塑性的记忆功能，我们将在大鼠的初级听觉皮层（A1）长期植入微电极，训练它们在有音调的情况下按杆喝水。我们将跟踪行为和可塑性的发展，并通过对广泛的纯音频率水平组合获得神经元放电和局部场电位响应的重复剖面，在一组动物中获得A1的完整功能图谱。与适当的对照组相比，训练后测试将评估记忆强度、对声音体验细节的记忆以及学习听觉提示回避任务的能力。如果基底核（NB）可以冥想A1的记忆功能，那么将音调与基底核刺激配对，诱导A1的可塑性和听觉记忆，应该可以提高记忆强度水平，保留声学细节，促进回避学习。研究结果对设计和实施治疗干预具有直接的翻译意义，包括修复儿童语音加工缺陷和学习理解人工耳蜗植入后的言语。修复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。

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.