Circuit mechanisms for temporal filtering in the auditory thalamus

描述（由申请人提供）：时间对听力至关重要——这一原则反映在负责听觉处理的神经回路中刺激锁定反应的时间精度高于视觉处理。然而，从听觉丘脑开始，继续到皮层，神经元表现出不再与刺激特征相锁定的尖峰模式。因此，丘脑回路将刺激锁定的代码转换为另一种尚未定义的代码的机制与所实现的精确的时间过滤操作密切相关。本研究旨在利用一种新的信息论方法，以新的精度阐明这些机制，该方法从记录的脉冲序列中获得时间过滤操作，并与切片电生理学和光激活离子通道相一致，针对特定细胞类型。这项工作可能与听觉假体的发展有关——就像早期的人工耳蜗没有利用听神经的声位映射一样，未来几代的听觉植入物可能会利用脑干和丘脑中输入的时间转换的知识。了解发生在丘脑的传入信息的深刻转变，可能会弥合脑干编码听觉信息和皮层中听觉刺激的高级表征之间的差距。内侧膝状核的丘状输入的光学控制也可能是听觉假体装置的另一种方法。

DESCRIPTION (provided by applicant): Timing is of central importance in hearing - this principle is reflected in the greater temporal precision of stimulus locked responses in neural circuits responsible for auditory processing as compared with visual processing. However, beginning with the auditory thalamus and continuing to cortex, neurons exhibit spiking patterns that are no longer phase-locked to stimulus features. The mechanisms by which the thalamic circuit transforms a stimulus-locked code into another, as-of-yet undefined code are thus intimately related to the precise temporal filtering operations that are implemented. This proposal seeks to elucidate those mechanisms with a new precision using a new information-theoretic method for deriving those temporal filtering operations from recorded spike trains in concert with slice electrophysiology and light-activated ion channels targeted to specific cell types. This work may have relevance to the development of auditory prostheses - in the same way that early cochlear implants did not take advantage of the tonotopic mapping of the auditory nerve, future generations of auditory implants may use knowledge about the temporal transformation of inputs that occurs in the brainstem and thalamus. Understanding the profound transformation of afferent information that occurs in the thalamus may bridge the gap between what is known about brainstem encoding of auditory information and what is not known about higher-level representations of auditory stimuli in the cortex. Optical control of collicular inputs to the medial geniculate nucleus may also represent an alternative method for auditory prosthetic devices. PUBLIC HEALTH RELEVANCE: The success of cochlear implants for treating deafness has been remarkable - yet this technology is ultimately fruitless for patients with lesions beyond the cochlea, so auditory brainstem implants have been in development since the 1970s to directly stimulate the next level of auditory processing. This proposal seeks to decipher the nature of the encoding of timing information in the auditory thalamus using a combination of advanced biophysical and computational techniques, so that future generations of auditory implants can benefit from this improved knowledge. The project also represents an application of optical control of neural activity in the auditory system, a potentially exciting avenue for future prosthetics research.