Functions of Associative Auditory Cortical Plasticity

联想听觉皮层可塑性的功能

• 批准号: 7934531
• 负责人: NORMAN M WEINBERGER
• 金额: $ 30.95万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-18 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7934531
• 关键词: Acoustics; Animals; Area; Auditory; Auditory area; Avoidance Learning; Basal Nucleus of Meynert; Behavior; Brain; Child; Clinical; Cochlear implant procedure; Communication; Complex; Comprehension; Control Groups; Cues; Custom; Development; FarGo; Frequencies; Functional Imaging; Goals; Hearing; Implant; Knowledge; Language; Learning; Longevity; Maps; Mediating; Memory; Microelectrodes; Neurons; Patients; Physiological; Process; Psychological reinforcement; Punishment; Rattus; Reporting; Research; Research Project Grants; Rewards; Role; Scalp structure; Signal Transduction; Specificity; Speech; Testing; Therapeutic Intervention; Training; Water; acoustic reflex; auditory comprehension; base; cholinergic; classical conditioning; design; experience; flexibility; improved; novel; phonology; public health relevance; relating to nervous system; remediation; response; sound

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.

描述（由申请人提供）：听觉理解以及听觉分析对于听力至关重要。对声音的理解需要持久的听觉记忆，即存储所学到的声音含义。听觉皮层的可塑性使得听觉记忆的丰富而复杂的领域得以实现。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，就像在联想学习期间一样。尽管学习诱发的皮质可塑性这一事实现已得到充分证实，但仅凭它无法充分理解听觉记忆的神经基础，也无法将基础知识有效应用于听力和交流的临床问题。确定皮质可塑性的记忆功能至关重要。该研究项目的目标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以下方式增强听觉记忆：（1）增强听觉记忆；（2）保留听觉细节；（3）促进听觉记忆的灵活运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控制可塑性的方法：（a）通过指导学习策略间接控制，（b）通过刺激基底核直接控制。为了测试这些假设并揭示联想可塑性的记忆功能，我们将训练老鼠的初级听觉皮层（A1）长期植入微电极，在有声音的情况下按杠取水。我们将跟踪行为和可塑性的发展，并通过获得神经元放电的重复分布和对各种纯音频率水平组合的局部场电位反应来获得动物亚群中 A1 的完整功能图。与适当的对照组相比，训练后测试将评估记忆强度、对声学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 NB 刺激配对以诱导 A1 可塑性和听觉记忆，应该会提高记忆强度、保留声音细节并促进回避学习。这些发现对治疗干预措施的设计和实施具有直接的转化意义，包括修复儿童语音处理缺陷以及学习人工耳蜗植入后理解言语。补救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（通过头皮录音或功能成像评估），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：听觉理解以及听觉分析对于听力至关重要，因为它可以识别包括语音在内的所有声音。该项目的结果将显着增进我们对大脑如何获取、表示、存储和利用听觉体验的理解。研究结果将与治疗干预措施的设计和实施直接相关，以实现和改善一般听觉和言语理解能力。