Thalamocortical mechanism underlying cortical temporal information processing for sound perception

在自然界中，经常有不止一种声音在短时间间隔内撞击鼓膜。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。前向掩蔽是一种行为现象，通常由双音刺激范式来衡量，它代表了对声音的感知如何被之前的声音抑制的能力。前向抑制是前向掩蔽的神经基础，在听觉皮质中有很好的特征，但其机制尚不清楚。在这里，我将重点放在将时间信息转换到大脑皮层的关键部位，特别是丘脑皮质(TC)在大脑皮层前向加工中的作用。由于丘脑下方有几个中继区，使用传统的双音模式不能描述完整动物的TC功能。我们采用了在体局灶电刺激听觉丘脑的方法，发现TC系统实现了皮层功能重构的同质促进和异质抑制机制。这里，我们假设TC系统以特定于输入的方式为皮质前向处理实现了中心环绕过程。这项工作设计了四个目标，将完成我们对TC在大脑皮层前向加工中作用的理解。我们首先利用经典的音调-音调对来确定丘脑皮质前向抑制的程度。第二个目的是通过在双音范式中用丘脑刺激代替前一个或后一个音调来测量TC对皮层前向抑制的直接贡献。第三个目的是通过成对的丘脑刺激建立皮层前向易化的发生，在该刺激中，前后两个刺激激活相同的TC输入。最后，我使用先进的技术--体内全细胞贴片和向记录的神经元注入GABA能药物，研究了皮质内兴奋和抑制电路在皮质前向处理中的作用。我们的数据提示TC转换在大脑皮层前向加工中起决定性作用。我们预计，TC系统锚定了一种声音感知的自我强化和环绕减弱的时间加工机制。这个重要的概念推进了我的长期目标，即揭开听觉中涉及的神经机制。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。

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.