Functional Organization of Auditory Corticofugal Circuits

项目摘要 路由和协调传感信息向下游区域的传播的能力是一个关键因素。 认知功能的关键特征。听觉皮层（ACtx）的深层产生了大量的 投射系统对多个下游大脑区域施加影响。脑下投射神经元 （SPNs）在层5 b内，其精心制作的树突状过程和广泛的轴突，长期以来一直是 被认为是典型的“广播”神经元，汇集来自上层皮层的输入， 向广泛的下游目标发出信号。我们最近的工作表明，至少有一些投射到 中脑还与丘脑、纹状体和杏仁核形成侧支。然而，现有的解剖学 这种投影系统的描述是缺乏的，在何种程度上SPN人口广播 与将听觉信号传输到多个下游目标相反， 单个离散区域是未知。尽管它们的影响广泛， 离皮质投射系统在很大程度上违背了体内生理学特征。因此， 发送到下游目标的传感信息仍有待建立。假设一些SPN 目标区域位于大脑的边缘系统和奖励系统内，评估非 与内部状态相关的感觉因素（如唤醒和运动）影响SPN的感觉加工 将信息传递给不同目标的群体。 最近的技术发展现在使得有可能在解剖学上表征输入/输出电路 除了能够在体内分离这些神经元以记录它们的特异性外， 对听觉处理的贡献。在这里，我们建议使用一组解剖学，光学和病毒 阐明小鼠ACtx中SPN群体的解剖连接性的方法，以了解其中的意义 这些SPN人口传达给下游地区的信息，并描述如何将这些信息 由内部状态调制。这些数据将为随后的R 01提供基础，R 01将确定 不同的ACtx投射可以影响感知并介导行为。

Project Summary The ability to both route and coordinate the propagation of sensory information to downstream areas is a critical feature of cognitive function. The deep layers of the auditory cortex (ACtx) give rise to a massive projection system that exerts influence over multiple downstream brain areas. Sub-cerebral projection neurons (SPNs) within layer 5b, with their elaborate dendritic processes and far-ranging axons, have long been regarded as canonical “broadcast” neurons, pooling inputs from the upper cortical layers and transmitting signals to widespread downstream targets. Our recent work has shown that at least some SPNs that project to the midbrain also collateralize in the thalamus, striatum, and amygdala. Nevertheless, existing anatomical descriptions of this projection system are lacking, and the extent to which SPN populations broadcast information to several downstream targets simultaneously, as opposed to transmitting auditory signals to a single discrete region is not known. Despite their widespread influence, the neurons contributing to this corticofugal projection system have largely defied in vivo physiological characterization. Thus, the kind of sensory information that is routed to downstream targets remains to be established. Given that some SPN target regions reside within the limbic and reward systems of the brain, it is also important to assess how non- sensory factors related to internal state (such as arousal and locomotion) affect sensory processing in SPN populations that route information to distinct targets. Recent technical developments now make it possible to anatomically characterize the input/output circuitry of specific neuron classes in addition to being able to isolate these neurons in vivo to document their specific contributions to auditory processing. Here, we propose to use a battery of anatomical, optical, and viral approaches to elucidate the anatomical connectivity of SPN populations in mouse ACtx, to understand what information these SPN populations convey to downstream areas, and to describe how this information can be modulated by internal state. These data will provide a foundation for a subsequent R01 that will determine how different ACtx projections can influence perception and mediate behavior.