Thalamocortical mechanism underlying cortical temporal information processing for sound perception

声音感知的皮质时间信息处理的丘脑皮质机制

• 批准号: RGPIN-2020-04591
• 负责人: YAN, JUN
• 金额: $ 2.04万
• 依托单位: University of Calgary
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=740061
• 关键词: Thalamocortical; mechanism; underlying; cortical; temporal

In nature, more than one sound often impinges upon the eardrum in short time-intervals. Thus, it is necessary to have the ability to focus on one sound and ignore others to enable social interactions involving oral communication. Forward masking, a behavioral phenomenon typically measured by the two-tone stimulus paradigm, represents the capacity of how perception of a sound is inhibited by preceding ones. Forward suppression, the neural basis of forward masking, is well characterized in the auditory cortex but its mechanism remains unclear. Here, I focus on the pivotal locus for the transformation of temporal information to the cortex, specifically, the thalamocortical (TC) role in cortical forward processing. Use of conventional two-tone paradigm cannot characterize the TC function in intact animals due to several relays below the thalamus. We used the approach of in vivo focal electrical stimulation of the auditory thalamus and discovered that the TC system implements a homo-facilitation & hetero-suppression mechanism for the remodeling of cortical function. Here we hypothesize that the TC system implements a center-surround process for cortical forward processing in an input-specific manner. This work, designed in four aims, will complete our understanding of the TC role in cortical forward processing. We first establish the degree of cortical forward suppression that originates in the thalamus using classical tone-tone pair. The second aim measures the direct TC contribution to cortical forward suppression by substituting thalamic stimulus for either the preceding or succeeding tone in the two-tone paradigm. The third aim establishes the occurrence of cortical forward facilitation by paired thalamic stimuli in which the preceding and succeeding stimuli activate identical TC inputs. Finally, I examine the role of intracortical excitatory and inhibitory circuitry in cortical forward processing using advanced techniques - in vivo whole cell patch and iontophoretic injection of GABAergic agent to recorded neurons. Our data prompt a decisive role of TC transformation in cortical forward processing. We anticipate that the TC system anchors a mechanism of a self-strengthening and surround-weakening temporal processing for sound perception. This important concept advances my long-term goal of uncovering the neural mechanism involved in hearing. It will also benefit research and education in the fields of hearing, physiology, psychology and neuroscience.

在自然界中，不止一种声音经常在短时间间隔内撞击耳膜。因此，有必要具备专注于一种声音而忽略其他声音的能力，以实现涉及口头交流的社会互动。前掩蔽（英语：Forward masking）是一种典型的由双音刺激范式测量的行为现象，代表了对一个声音的感知如何被前一个声音抑制的能力。前向抑制是前向掩蔽的神经基础，在听觉皮层中有很好的特征，但其机制尚不清楚。在这里，我专注于关键的轨迹转换的时间信息的皮层，具体地说，丘脑皮质（TC）的作用，在皮层前向处理。使用传统的双音范式不能表征的TC功能在完整的动物，由于丘脑下的几个继电器。我们采用在体局部电刺激听觉丘脑的方法，发现TC系统对皮层功能的重塑实施同源易化和异源抑制机制。在这里，我们假设TC系统实现了一个中央环绕的过程中，皮层前向处理的输入特定的方式。这项工作，设计在四个目标，将完成我们的理解TC的作用，在皮层前向处理。我们首先使用经典的音-音对建立起源于丘脑的皮质前向抑制的程度。第二个目标是通过用丘脑刺激代替双音范式中的前音或后音来测量TC对皮质前向抑制的直接贡献。第三个目标建立了成对的丘脑刺激，其中之前和之后的刺激激活相同的TC输入的皮质向前促进的发生。最后，我检查皮质内的兴奋和抑制电路在皮质前向处理的作用，使用先进的技术-在体内的全细胞补丁和离子电渗注射GABA能剂记录的神经元。我们的数据提示TC转换在皮质前向处理中发挥决定性作用。我们预计，TC系统锚定的机制，自我加强和周围弱化的时间处理的声音感知。这个重要的概念推进了我的长期目标，即揭示与听觉有关的神经机制。它还将有利于听力、生理学、心理学和神经科学领域的研究和教育。