Functional organization of the auditory corticocollicular system

听觉皮质皮质系统的功能组织

• 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
• 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

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.

项目总结 从退化的声音中破译意义的能力对日常听力至关重要。一个关键战略，以提取 隐藏信号是将存储的声学表示与输入的声流相结合。这样的顶端- 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，这样的中断 这些过程可能与自闭症和阅读障碍等障碍有关。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 从听皮质到下丘(IC)的大规模下行通路分析 对于自上而下的调制非常重要。尽管这条途径已被证明对许多过程是关键的 对于听觉感知来说很重要，但它如何支持如此多样化的功能尚不清楚。 在上一个资助期，我们发现了这条途径出人意料的异质性。为 例如，我们观察到这一通路起源的两个皮质层中的神经元，第5层(L5) 和第6层(L6)，具有不同的生理、形态和连通性模式。L5神经元直接接受 丘脑传入，刺激时爆发，并向外侧皮质(LC)发送含有巨型终末的投射 是IC的。L6神经元接受稀疏的局部输入，但样本来自皮质的广泛区域，并以小的形式结束 位于LC远端边缘的终末。这些数据表明，L5神经元向 L6神经元通过广泛的多感觉整合来调节LC功能。我们还发现， 在LC中，皮质小丘投射与周期性的神经化学簇(“斑块”和“基质”)交错排列。 并且该补丁/矩阵系统的存在实际上管理到和来自该结构的所有输入和输出。 这些调查结果提出了几个问题，这些问题将在目前的提案中得到解决。首先，如何 L5/L6系统与组成LC？的神经化学和连接嵌合体的界面要解决这个问题 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，然后使用 依赖Cre的跨突触追踪的新形式，用于定位L5或L6起始和结束的平行通路 在LC的众多目标中的一个。第二，我们将研究L5和L6终末对LC神经元的影响 使用光学和电生理方法来确定它们的相对影响和几何形状 投入。第三，我们将通过成像L5和L6中的轴突来确定L5和L6向LC发送了哪些消息 基于微棱镜的双光子成像方法对听觉和非听觉刺激的响应 在清醒的小鼠身上。因此，我们可以确定L5和L6是否向LC发送不同的消息，以及消息是否 在补丁/矩阵地形上有所不同。因此，通过利用补丁/矩阵组织来解析 LC的输入和输出密密麻麻，这项工作将阐明自上而下的机制 听觉系统中的调制。在这样做的过程中，它将提供一个理解疾病的范例 自上而下/自下而上的整合中断，如诵读困难和自闭症。

项目成果

Effect of temperature on FAD and NADH-derived signals and neurometabolic coupling in the mouse auditory and motor cortex.

• DOI: 10.1007/s00424-017-2037-4
• 发表时间: 2017-12
• 期刊: Pflugers Archiv : European journal of physiology
• 作者: Ibrahim BA;Wang H;Lesicko AMH;Bucci B;Paul K;Llano DA
• 通讯作者: Llano DA

Two-photon microscope using a fiber-based approach for supercontinuum generation and light delivery to a small-footprint optical head.

双光子显微镜使用基于光纤的方法来生成超连续谱并将光传输到小型光学头。

• DOI: 10.1364/ol.381571
• 发表时间: 2020
• 期刊: Optics letters
• 影响因子: 3.6
• 作者: Zhao,Youbo;Maguluri,Gopi;DanielFerguson,R;Tu,Haohua;Paul,Kush;Boppart,StephenA;Llano,DanielA;Iftimia,Nicusor
• 通讯作者: Iftimia,Nicusor

Pharmacological inhibition of STriatal-Enriched protein tyrosine Phosphatase by TC-2153 reduces hippocampal excitability and seizure propensity.

TC-2153对富含纹状体的蛋白酪氨酸磷酸酶的药理抑制作用降低了海马兴奋性和癫痫发作倾向。

• DOI: 10.1111/epi.17192
• 发表时间: 2022-05
• 期刊: EPILEPSIA
• 影响因子: 5.6
• 作者: Walters, Jennifer M.;Kim, Eung Chang;Zhang, Jiaren;Jeong, Han Gil;Bajaj, Archit;Baculis, Brian C.;Tracy, Gregory C.;Ibrahim, Baher;Christian-Hinman, Catherine A.;Llano, Daniel A.;Huesmann, Graham R.;Chung, Hee Jung
• 通讯作者: Chung, Hee Jung

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

• DOI: 10.1016/j.arr.2018.04.001
• 发表时间: 2018-07
• 期刊: AGEING RESEARCH REVIEWS
• 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.

Descending projections to the auditory midbrain: evolutionary considerations.

• DOI: 10.1007/s00359-022-01588-5
• 发表时间: 2023-01
• 期刊: Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology