Microcircuit Architecture of Top-Down Cortical Modulation of Auditory Pathways

描述（由申请人提供）：听觉系统中的信息处理涉及信号的双向流动。起源于感觉外周的声学信号（即，内耳）行进到大脑皮层并形成自下而上的通路。始发的信号 大脑皮层中的信号以相反的方向传递，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，但自上而下通路的细胞特性和突触连接（或电路）在很大程度上仍然未知。本研究的重点是研究脑干听觉皮层投射到下丘的神经元的内在特性和微电路结构。或者初步结果表明，IC投射神经元位于两个不同的皮质层： 层5B和层7。通过结合使用逆行标记技术和成对的全细胞记录，我们将表征神经元的内在生理特性， 这些自上而下的平行路径。我们将使用激光扫描光刺激来确定自上而下的皮质丘神经元的底层微电路结构。我们的初步研究结果表明，听觉皮质丘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。 去甲肾上腺素能和其他调节途径调节Ih，这表明听觉系统中自上而下途径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层微电路结构的音调依赖性。这一贡献是重要的，因为它是理解听觉系统自上而下信号起源的功能网络基础的第一个sep。在我们看来，所提出的方法是创新的，因为它结合了自上而下的听觉皮层神经元的解剖识别，电生理特性，微电路映射和在体功能成像技术，以了解自上而下的听觉皮层电路的tonotopic组织。

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.