Cortical circuits for spectro-temporal integration of multi-frequency sounds

项目总结 在日常生活中，即使面对多个声源，我们的大脑也会将频率成分捆绑在一起 属于同一来源并识别各个声音对象的。在人类中，光谱的整合 组成单一声音知觉的组件依赖于它们开始计时的精确同步，而这 分组在我们对语言的感知中起着至关重要的作用。在我们正在进行的家长资助(R01 DC017516)中，我们 已经确定小鼠的次级听觉皮质A2是一个多频整合的位点，其 依赖于同步的声音反应反映了人类的知觉绑定。然而，电路机制 A2神经元如何跨平行听觉通道整合信息以实现连贯 人们的认知仍然是未知的。二次感觉皮层通常被认为是接收到 来自初级皮质的输入。有趣的是，最近跨感觉模式的研究表明，次要的 大脑皮层也可以绕过初级皮质区，直接从外周接受感觉输入。在 听觉系统，最近的一篇论文和我们的初步数据都表明，A2接受来自 初级听觉丘脑(内侧膝状核腹侧支：MGV)。这些结果需要 重新考虑作为高级皮质区域特殊功能基础的感觉通路。 在这个拟议的项目中，我们将用解剖学和统计学方法描绘MGV-A2的上升途径 电生理技术，以了解其对A2回路的综合功能的贡献。我们的 具体目标是：1)使用示踪剂识别MGV-A2通路上游的下丘亚群 注射和2)利用光遗传学确定MGV输入对A2声音表征的贡献 在活体电生理记录期间。这些目标将扩大家长研究的范围，即 重点放在A2内整合多频率声音的大脑皮层回路。上升界的解剖 到达A2的通路将提供对塑造A2声音表示和 为理解实现语言交流的“功能绑定”电路提供一个步骤。穿过 拟议的毕业后增刊，米歇尔·加西亚女士将与她的导师Dr。 加藤，接受尖端神经科学技术、听觉系统神经科学和 写作/沟通能力。加西亚女士的长期目标是参加一个神经科学博士项目并继续 她作为一名独立科学家在学术界的职业生涯。这个补充项目将有助于她的事业发展 通过让她做好准备，以研究生的身份从事神经科学研究以及以后的工作。

PROJECT SUMMARY In our daily life, even in the face of multiple sound sources, our brain binds together frequency components that belong to the same source and recognizes individual sound objects. In humans, the integration of spectral components into single sound perception relies on the precise synchrony of their onset timings, and this grouping plays a critical role in our perception of language. In our ongoing parent grant (R01 DC017516), we have identified the mouse secondary auditory cortex, A2, as a locus of multi-frequency integration, whose synchrony-dependent sound responses mirror perceptual binding in humans. However, the circuit mechanisms underlying how A2 neurons integrate information across parallel auditory channels to achieve coherent perception remain unknown. Secondary sensory cortices are generally considered to receive pre-processed inputs from the primary cortices. Interestingly, recent studies across sensory modalities suggest that secondary cortices may also receive sensory inputs directly from the periphery, bypassing primary cortical areas. In the auditory system, both a recent paper and our preliminary data showed that A2 receives direct inputs from the primary auditory thalamus (ventral division of the medial geniculate nucleus: MGv). These results require reconsideration of the sensory pathways that underlie the specialized functions of higher-order cortical areas. In this proposed project, we will delineate the MGv-A2 ascending pathway using anatomical and electrophysiological techniques to understand its contribution to the integrative function of A2 circuits. Our specific goals aim to 1) identify the inferior colliculus subdivision upstream to the MGv-A2 pathway using tracer injections and 2) determine the contribution of MGv inputs to A2 sound representations using optogenetics during in vivo electrophysiological recordings. These aims will expand the scope of the parent study, which focuses on the cortical circuits within A2 that integrate multi-frequency sounds. Dissection of the ascending pathways that reach A2 will provide insights into the mechanisms that shape A2 sound representations and provide a step towards understanding the “feature binding” circuits that enable verbal communication. Through the proposed Post-baccalaureate Supplement, Ms. Michellee Garcia will work closely with her mentor, Dr. Kato, to receive training in cutting-edge neuroscience techniques, auditory systems neuroscience, and writing/communication skills. Ms. Garcia’s long-term goal is to join a neuroscience Ph.D. program and continue her career in academia as an independent scientist. This supplement project will help her career development by preparing her to pursue neuroscience research as a graduate student and beyond.