Dynamic Regulation of Tuning in Adult Auditory Cortex

描述（由申请人提供）：学习和记忆是绝对必要的听力。如果没有这些声音，就不可能理解，因为无法获得或存储听觉信息，也不可能识别以前听到的声音。该研究项目的长期目标是发现使声音获得意义的神经机制。初级听觉皮层（A1）被认为是听觉信息获取和存储的场所。一般来说，行为相关声音的编码作为声学表征的整体功能重塑的一部分而得到加强。例如，当一个音调成为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，同时削弱其他频率的编码。调谐移位可以增加A1中信号表征的面积，并且增益的量与线索的获得重要性水平及其记忆强度成正比。这种表征可塑性（RP）似乎是听觉记忆的基础，因为它具有与记忆本身相同的属性。直接或通过配对音调与胆碱能基底核（NBstm）的刺激在A1中的mAChR的参与足以（a）产生RP，（B）实际植入特定的行为听觉记忆，以及（c）增加神经同步（NSync）。此外，增加同步预测RP在A1和听觉记忆。因此，声音可以通过增加神经同步来获得意义，这使它们在与目标结构沟通和加强自身表征方面更有效。该项目的具体目标是确定在信号呈现期间增加NSynch（伽马波段振荡和单位协方差）是否可以加强和增加听觉记忆的特异性和/或增强RP。将在听觉恐惧和奖励任务中训练大鼠，同时通过增加响度或短暂并发NBstm来增强信号音诱导的神经同步。研究将确定增加NSync是否可以增强记忆强度和特异性，使用定制设计的训练方案，产生适度水平的RP和记忆。如果这些实验揭示了神经同步作为一种机制，足以加强和/或产生特定的听觉记忆，那么这个项目将开辟一条听觉理解障碍的补救途径。

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.