Functional Organization of Auditory Corticofugal Circuits

项目摘要 将感觉信息发送和协调传播到下游区域的能力是一种 认知功能的关键特征。听觉皮质的深层(ACTx)产生大量的 对多个下游大脑区域施加影响的投影系统。大脑下投射神经元 (SPN)位于5b层，具有复杂的树突和广泛的轴突，长期以来 被认为是典型的“广播”神经元，汇集上层大脑皮层的信息并传输 向广泛的下游目标发出信号。我们最近的研究表明，至少有一些SPN投射到 中脑也在丘脑、纹状体和杏仁核形成侧支。然而，现有的解剖学 缺乏对这一预测系统的描述，以及SPN人口广播的程度 信息同时发送到几个下游目标，而不是将听觉信号传输到 单一的离散区域是未知的。尽管它们有广泛的影响，但对此做出贡献的神经元 皮质激素投射系统在很大程度上违背了体内的生理特性。因此，这种 被传送到下游目标的感觉信息仍有待确定。鉴于一些SPN 靶区位于大脑的边缘和奖赏系统内，评估非 与内部状态相关的感觉因素(如唤醒和运动)影响孤束核的感觉加工 将信息发送到不同目标的群体。 最近的技术发展现在使从解剖学上描述输入/输出电路成为可能 除了能够在体内分离这些神经元以记录其特定的 对听觉处理的贡献。在这里，我们建议使用一组解剖、光学和病毒 阐明小鼠ACTx中SPN群体的解剖连接的方法，以了解什么 这些SPN种群将信息传递给下游地区，并描述这些信息是如何 受内部状态调制的。这些数据将为后续的R01奠定基础，R01将决定如何 不同的ACTx投影可以影响感知和调节行为。

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.