The role of the thalamic reticular nucleus in the temporal processing of medial g

描述(由申请人提供)：时间线索对言语感知至关重要。了解时变信号是如何在前脑中转换的，对于了解语音等与生物相关的信号是如何在听觉皮质中产生的至关重要。听觉丘脑是所有到达听觉皮质的信息的关键检查点。尽管进行了几十年的科学研究，但它的作用仍然不得而知。理解丘脑作用的一个关键可能在于它与一种密切相关的神秘结构--丘脑网状核(TRN)的相互作用。我假设听觉丘脑起着时间过滤器的作用，而过滤特性是由丘脑网状核(TRN)通过控制放电模式，在紧张性和爆发性尖峰之间切换丘脑皮质神经元而主动调制的。这些拟议的研究将探讨听觉丘脑在TRN刺激和不刺激TRN的情况下对上升信息的影响，并阐明丘脑对复杂输入进行时间过滤的机制。使用最近开发的包含从下丘(IC)到听觉丘脑(背侧和腹侧内侧膝状体(MGB)的部分)的完整投射的脑片制备，我们将系统地干扰TRN以评估其对丘脑-丘脑-皮质传递的影响。在这项工作中，我们将使用激光光刺激、黄素蛋白自发荧光成像和全细胞膜片钳来研究TRN对MGB时间过滤的影响的细胞机制。这项工作如果成功，将使我们能够深入了解听觉系统如何处理复杂的信号，并将影响未来为听力损失或其他沟通障碍患者设计的治疗策略，如假肢装置。

DESCRIPTION (provided by applicant): Temporal cues are critical for speech perception. Understanding how time-varying signals are transformed in the forebrain will be critical for understanding how the representations of biologically-relevant signals, such as speech, are created in the auditory cortex. The auditory thalamus is a critical checkpoint for all information that reaches the auditory cortex. Despite many decades of scientific investigation, its role has remained unknown. One key to understanding the role of the thalamus likely lies in its interactions with a closely related and mysterious structure known as the thalamic reticular nucleus (TRN). I hypothesize that the auditory thalamus acts as a temporal filter and that the filtering properties are actively modulated by the thalamic reticular nucleus (TRN) by controlling the firing mode, switching thalamocortical neurons between tonic and burst spiking. The proposed studies will address the impact the auditory thalamus has on ascending information with and without TRN stimulation as well as elucidate the mechanisms of thalamic temporal filtering of complex inputs. Using a recently developed brain slice preparation that contains intact projections from the inferior colliculus (IC), to the auditory thalamus (portions of both dorsal and ventral medial geniculate body, or MGB), to the AC we will systematically perturb the TRN to assess its impact on colliculo- thalamo-cortical transmission. We will use laser photostimulation, flavoprotein autofluorescence imaging and whole cell-patch clamp in this work to investigate the cellular mechanisms of the impact of the TRN on temporal filtering by the MGB. This work, if successful, will allow us to gain insights as to how the auditory system processes complex signals, and will impact future design of therapeutic strategies, such as prosthetic devices, for patients with hearing loss or other disorders of communication.