Functional organization of the auditory corticocollicular system

听觉皮质皮质系统的功能组织

基本信息

批准号：
10584167
负责人：
DANIEL A LLANO
金额：
$ 37.62万
依托单位：
UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-04-01 至 2028-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10584167
关键词：
Acoustics Address Anatomy Area Auditory Auditory Perception Auditory area Auditory system Axon Behavioral Brain Brain region Cells Chemicals Classification Cognition Disorders Collection Corpus striatum structure Data Dendrites Disease Distal Dyslexia Electrophysiology (science)Environment Funding Geometry Goals Hearing Heterogeneity Image Inferior Colliculus Language Lateral Location Machine Learning Maps Measures Mediating Mental Depression Metabolic Modernization Molecular Morphology Mus Neurons Optics Organizational Productivity Output Pathway interactions Pattern Perception Periodicals Physiological Play Population Process Property Role Sampling Secure Sensory Signal Transduction Slice Source Spatial Distribution Speech Stimulus Stream Structure Support System Synapses System Techniques Thalamic structure Work auditory pathway autism spectrum disorder awake cell type experience experimental study hearing impairment imaging approach machine learning algorithm molecular marker mosaic mouse model multisensory neurochemistry novel postsynaptic response sensory integration sensory stimulus sensory system sound striosome tool two-photon virtual

项目摘要

PROJECT SUMMARY The ability to decipher meaning from degraded sounds is critical for everyday hearing. A key strategy to extract buried signals is to integrate stored acoustic representations with the incoming sound stream. Such top- down/bottom-up interaction appears to be a fundamental feature in sensory systems. Indeed, disruptions of such processes may be involved in disorders such as autism and dyslexia. Unfortunately, little is known about the mechanisms by which top-down information modulates sensory function. Here, we propose a circuit-level analysis of a massive descending pathway from the auditory cortex to the inferior colliculus (IC) which is thought to be important for top-down modulation. Although this pathway has been shown to be critical for many processes important for auditory perception, how it supports such diversity of function is not known. During the last funding period, we uncovered an unexpected degree of heterogeneity in this pathway. For example, we observed that neurons in the two cortical layers from which this pathway is derived, layer 5 (L5) and layer 6 (L6), have distinct physiological, morphological and connectivity patterns. L5 neurons receive direct thalamic input, burst when stimulated and send projections containing giant terminals to the lateral cortex (LC) of the IC. L6 neurons receive sparse local input, but sample from a broad area of the cortex and end in small terminals on the distal rim of the LC. These data suggest that L5 neurons send a rapid and secure signal to the LC, while L6 neurons modulate LC function based on broad multisensory integration. We also found that the corticocollicular projections interdigitate with periodic neurochemical clusters (“patches” and “matrix”) in the LC and that the presence of this patch/matrix system governs virtually all input and output to and from this structure. These findings raise several questions that will be addressed in the current proposal. First, how does the L5/L6 system interface with the neurochemical and connectional mosaic comprising the LC? To address this question, we will use machine learning tools to parse the neurochemical cell classes in the LC, and then use a novel form of Cre-dependent trans-synaptic tracing to map parallel pathways originating in L5 or L6 and ending at one of the many targets of the LC. Second, we will examine the impact of L5 and L6 terminals on LC neurons using optical and electrophysiological approaches to determine the relative impacts and geometry of these inputs. Third, we will determine what messages are sent by L5 and L6 to the LC by imaging their axons in response to auditory and non-auditory stimulation using a novel microprism-based two-photon imaging approach in awake mice. We can thus determine if L5 and L6 send distinct messages to the LC, and whether the messages vary across the patch/matrix topography. Therefore, by leveraging the patch/matrix organization to parse the dense thicket of inputs and outputs to and from the LC, this work will shed light on mechanisms of top-down modulation in the auditory system. In doing so, it will provide a paradigm for understanding diseases involving disruptions in top-down/bottom-up integration, such as dyslexia and autism.

项目概要从退化的声音中解读含义的能力对于日常听力来说至关重要，这是提取含义的关键策略。隐藏信号是将存储的声学表示与输入的声音流集成。向下/自下而上的相互作用似乎是感觉系统的一个基本特征。事实上，这种破坏是感觉系统的一个基本特征。不幸的是，人们对此知之甚少。自上而下的信息调节感觉功能的机制在这里，我们提出了一种电路级的机制。分析从听觉皮层到下丘（IC）的大量下降通路，该通路被认为对于自上而下的调节很重要，尽管该途径已被证明对许多过程至关重要。对于听觉感知很重要，但它如何支持这种功能多样性尚不清楚。在上一个资助期间，我们发现了这条途径中意想不到的异质性程度。例如，我们观察到该通路所源自的两个皮质层中的神经元，即第 5 层 (L5) 和第 6 层 (L6)，具有不同的生理、形态和连接模式，直接接收 L5 神经元。丘脑输入，受到刺激时爆发，并将包含巨型末端的投射发送到外侧皮层 (LC) IC 的 L6 神经元接收稀疏的局部输入，但从皮层的广阔区域进行采样并以较小的区域结束。这些数据表明 L5 神经元向 LC 发送快速且安全的信号。 LC，而 L6 神经元基于广泛的多感觉整合来调节 LC 功能。皮质丘状投射与 LC 中的周期性神经化学簇（“斑块”和“矩阵”）相互交错并且该贴片/矩阵系统的存在几乎控制了进出该结构的所有输入和输出。这些发现提出了当前提案将解决的几个问题：首先，如何进行。 L5/L6 系统与包含 LC 的神经化学和连接嵌合体接口？问题，我们将使用机器学习工具来解析 LC 中的神经化学细胞类别，然后使用 Cre 依赖性跨突触追踪的新形式，用于绘制源自 L5 或 L6 并结束的平行通路其次，我们将检查 L5 和 L6 末端对 LC 神经元的影响。使用光学和电生理学方法来确定这些的相对影响和几何形状第三，我们将通过对 L5 和 L6 的轴突进行成像来确定 L5 和 L6 向 LC 发送哪些消息。使用基于微棱镜的新型双光子成像方法对听觉和非听觉刺激做出响应因此，我们可以确定 L5 和 L6 是否向 LC 发送不同的消息，以及这些消息是否相同。因此，通过利用补丁/矩阵组织来解析。 LC 的输入和输出密集，这项工作将揭示自上而下的机制在此过程中，它将为理解涉及疾病的范例提供一个范例。自上而下/自下而上整合的破坏，例如阅读障碍和自闭症。

项目成果

期刊论文数量（13）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Hitting The Right Spot: NMDA Receptors in the Auditory Thalamus May Hold the Key to Understanding Schizophrenia.

击中正确位置：听觉丘脑中的 NMDA 受体可能是理解精神分裂症的关键。

DOI：
发表时间：
2020
期刊：
影响因子：
0
作者：
Xiao, Gang;Llano, Daniel A
通讯作者：
Llano, Daniel A

Auditory system dysfunction in Alzheimer disease and its prodromal states: A review.

阿尔茨海默病及其前驱状态的听觉系统功能障碍：综述。

DOI：
发表时间：
2018-07
期刊：
影响因子：
13.1
作者：
Swords, Gabriel M;Nguyen, Lydia T;Mudar, Raksha A;Llano, Daniel A
通讯作者：
Llano, Daniel A

Increased pyramidal and VIP neuronal excitability in rat primary auditory cortex directly correlates with tinnitus behaviour.

大鼠初级听觉皮层锥体和 VIP 神经元兴奋性的增加与耳鸣行为直接相关。

DOI：
发表时间：
2023-06
期刊：
影响因子：
0
作者：
Ghimire, Madan;Cai, Rui;Ling, Lynne;Brownell, Kevin A;Hackett, Troy A;Llano, Daniel A;Caspary, Donald M
通讯作者：
Caspary, Donald M

Anatomical characterization of subcortical descending projections to the inferior colliculus in mouse.

小鼠下丘皮质下下降投影的解剖学特征。

DOI：
发表时间：
2017-03-01
期刊：
影响因子：
0
作者：
Patel, Mili B;Sons, Stacy;Yudintsev, Georgiy;Lesicko, Alexandria M H;Yang, Luye;Taha, Gehad A;Pierce, Scott M;Llano, Daniel A
通讯作者：
Llano, Daniel A

Does hearing loss lead to dementia? A review of the literature.

听力损失会导致痴呆吗？