Microcircuit Architecture of Top-Down Cortical Modulation of Auditory Pathways

描述(申请人提供)：听觉系统中的信息处理涉及信令的双向流动。起源于感觉外周(即内耳)的声音信号传播到大脑皮层，形成自下而上的通路。发出的信号 在大脑皮层中以相反的方向传输，形成自上而下的通路。虽然许多解剖学和功能研究都集中在自下而上的通路上，但自上而下的通路的细胞特性和突触连接(或电路)在很大程度上仍不清楚。这一建议集中在听觉脑干中投射到下丘(IC)的听觉皮质神经元的内在特性和微电路结构。或初步结果显示，IC投射神经元位于两个不同的皮质层： 通过结合使用逆行标记技术和配对的全细胞记录，我们将表征神经元的内在生理特性。 这些平行的自上而下的路径。我们将使用激光扫描光刺激来确定自上而下皮质小脑神经元的潜在微电路结构。我们的初步结果显示，听觉皮质小脑神经元表现出明显的超极化激活电流(Ih)，这限制了兴奋性输入产生尖峰输出的能力。 去甲肾上腺素和其他调节通路调节iH，表明听觉系统中自上而下通路的兴奋性受大脑状态的调节。最后，在活体功能成像的帮助下，我们将确定初级听觉皮质微电路结构的紧张性依赖。这一贡献意义重大，因为它是第一次理解听觉系统自上而下信号产生的功能网络基础。我们认为，提出的方法是创新的，因为它结合了自上而下听觉皮质神经元的解剖学识别、电生理特征、微电路标测和活体功能成像技术，以了解听觉皮质自上而下回路的立位组织。 与公共健康相关：来自大脑皮层的自上而下的通路在调节与行为相关的听觉信号的皮层下处理方面发挥着重要作用。这一建议旨在了解皮层生理学的直视组织和下丘产生自上而下信号的基础电路。本研究将对理解自上而下的信号通路在健康和病理性听觉加工中的整合和调控具有重要意义。

DESCRIPTION (provided by applicant): Information processing in the auditory system involves a bidirectional flow of signaling. Acoustic signals that originate in the sensory peripher (i.e., inner ear) travel to the cerebral cortex and form the bottom-up pathway. Signals originating in the cortex are transmitted in the reverse direction and form the top-down pathway. While many anatomical and functional studies have focused on the bottom up pathway, the cellular properties and synaptic connectivity (or circuitry) of the top-down pathway remain largely unknown. This proposal focuses on the intrinsic properties and microcircuit architecture of auditory cortical neurons that project to the inferior colliculus (IC) in the auditory brainstem. Or preliminary results show that IC-projecting neurons are localized in two different cortical layers: layer 5B and layer 7. Through the combined use of retrograde labeling techniques and paired whole cell recordings we will characterize the intrinsic physiological properties of the neurons in these parallel top-down pathways. We will use laser- scanning photostimulation to determine the underlying microcircuit architecture of top-down corticocollicular neurons. Our preliminary results show that auditory corticocollicular neurons exhibit pronounced hyperpolarization-activated currents (Ih), which limits the ability of excitatory inputs to generate spiking outputs. Noradrenergic and other modulatory pathways regulate Ih, suggesting that the excitability of top-down pathways in the auditory system are modulated by brain state. Finally, with the aid of in vivo functional imaging we will determine the tonotopic dependence of microcircuit architecture in primary auditory cortex. This contribution is significant because it is the first sep in understanding the functional network basis for the genesis of top-down signals to the auditory system. The proposed approach is innovative, in our opinion, because combines anatomical identification of top-down auditory cortical neurons, electrophysiological characterization, microcircuit mapping and in vivo functional imaging techniques to understand the tonotopic organization of top-down circuits in the auditory cortex. PUBLIC HEALTH RELEVANCE: Top-down pathways from the cortex play an important role in modulating subcortical processing of behaviorally relevant auditory signals. This proposal aims to understand the tonotopic organization of cortical physiology and circuitry underlying the generation of top-down signals to the inferior colliculus. This research will significantly contribte to the understanding of the integration and regulation of top-down signaling pathways in healthy and pathological auditory processing.