Dynamic Regulation of Tuning in Adult Auditory Cortex

描述(申请人提供)：学习和记忆对听力是绝对必要的。如果没有它们，理解将是不可能的，因为无法获取或存储任何听觉信息，也不可能识别以前听到的声音。这项研究项目的长期目标是发现使声音获得意义的神经机制。初级听觉皮质(A1)被认为是获取和存储听觉信息的场所。总体而言，行为相关声音的编码作为声学表征整体功能重建的一部分得到加强。例如，当一个音调变成奖励或厌恶刺激的信号时，频率调谐向信号频率移动，加强其编码，而削弱其他频率的编码。调谐变化可以增加A1中信号表示的面积，并且增益量与线索获得的重要性水平及其记忆强度成正比。这种表征可塑性(RP)似乎是听觉记忆的底物，因为它与记忆本身具有相同的属性。直接或通过刺激胆碱能基底核(NBstm)使A1中的mAChR参与足以(A)产生RP，(B)实际上植入特定的行为听觉记忆，(C)增加神经同步性(NSync)。此外，同步性的增强预示着A1和听觉记忆中的RP。因此，声音可能通过增加神经同步性而获得意义，这使它们在与目标结构沟通和加强自己的表征方面更加有效。这个项目的具体目的是确定在信号呈现过程中增加NSynch(伽马带振荡和单位协方差)是否可以增强和提高听觉记忆的特异性，和/或增强RP。大鼠将接受听觉恐惧和奖励任务的训练，而信号音调诱导的神经同步性则通过增加响度或短暂的并行NBstm来增强。研究将确定增加NSync是否可以增强记忆强度和特异性，使用定制的训练方案，产生适度水平的RP和记忆。如果这些实验发现神经同步性是一种足以增强和/或产生特定听觉记忆的机制，那么这个项目将为修复听觉理解障碍开辟一条道路。

DESCRIPTION (provided by applicant): Learning and memory are absolutely essential to hearing. In their absence, comprehension would be impossible because no auditory information could be acquired or stored, and the recognition of previously heard sounds would be impossible. The long-term objectives of this research project are to discover the neural mechanisms that enable sounds to acquire meaning. The primary auditory cortex (A1) has been identified as a site for the acquisition and storage of auditory information. In general, encoding of behaviorally relevant sounds is strengthened as part of an overall functional remodeling of acoustic representation. For example, when a tone becomes a signal for rewarding or aversive stimuli, frequency tuning shifts toward or to the signal frequency, strengthening its encoding while weakening that of other frequencies. Tuning shifts can increase the area of signal representation in A1, and the amount of gain is directly proportional to both the cue's level of acquired importance and its memory strength. Such representational plasticity (RP) appears to be a substrate of auditory memory because it has the same attributes as memory itself. Engagement of mAChR's in A1 directly or by pairing tone with stimulation of the cholinergic nucleus basalis (NBstm) is sufficient to (a) produce RP, (b) actually implant specific behavioral auditory memory, and (c) increase neural synchrony (NSync). Further, increased synchrony predicts both RP in A1 and auditory memory. Thus, sounds may gain meaning via increased neural synchrony, which gives them greater effectiveness in communicating with target structures and strengthening their own representations. The specific aims of this project are to determine if increasing NSynch (gamma band oscillations and unit co-variances) during signal presentation can strengthen and increase the specificity of auditory memory, and/or enhance RP. Rats will be trained in auditory fear and reward tasks while a signal tone's induced neural synchronization is boosted via increasing loudness or brief concurrent NBstm. Studies will determine if increasing NSync can enhance memory strength and specificity, using custom designed training protocols that produce a modest level of RP and memory. If these experiments uncover neural synchrony as a mechanism sufficient to strengthen and/or produce specific auditory memory, then this project will have opened a pathway for remediation of auditory comprehension disorders.