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Cortical circuits for the integration of parallel short-latency auditory pathways

用于整合并行短延迟听觉通路的皮层电路

基本信息

批准号：
10524362
负责人：
Hiroyuki Kato
金额：
$ 153.83万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-07-15 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10524362
关键词：
Acoustics Affect Anatomy Auditory Auditory area Auditory system Automobile Driving Behavior Behavioral Brain Cell Nucleus Cerebral cortex Cochlear nucleus Data Development Electrophysiology (science)Foundations Functional disorder Future Gene Expression Geniculate body structure Goals Head Hearing problem In Vitro Inferior Colliculus Knowledge Label Link Maps Medial Mediating Modality Mus Neurons Neurosciences Pathway interactions Perception Peripheral Presynaptic Terminals Research Role Running Sensory Shapes Slice Stimulus Structure Synapses Testing Thalamic structure Time Transgenic Mice Whole-Cell Recordings Work anatomical tracing auditory pathway auditory processing auditory thalamus awake cell type experience experimental study in vivo inhibitory neuron insight multisensory neural circuit novel operation optogenetics patch clamp preservation response sensory integration sound

项目摘要

PROJECT SUMMARY How our brain achieves coherent perception by integrating information from parallel sensory pathways distributed across space and time remains a central question in neuroscience. In the auditory system, sound information reaches the cortex via the lemniscal (“primary”) and non-lemniscal (“secondary”) pathways. The non-lemniscal pathways have often been described as slower integrators of multi-sensory information, in contrast to the roles of the lemniscal pathways as fast and reliable relays for sound inputs. However, the contribution of the non-lemniscal pathways in driving fast cortical responses and how they interact with the lemniscal pathways during sound processing are still matters of debate. Our preliminary electrophysiology experiments show that layer 6 (L6) of not only the primary but also the secondary auditory cortex receives sound inputs whose latency can be shorter than the L4 lemniscal inputs. Surprisingly, our retrograde tracing demonstrates that this short-latency L6 input originates from the non-tonotopic parts of the auditory thalamus, supporting the role of the non-lemniscal pathway in fast sensory processing. Building on this exciting finding, we will combine anatomical tracing, in vitro/in vivo electrophysiology, optogenetics, and behavior to delineate this non-classical pathway and determine how it interacts with the lemniscal pathway to regulate cortical sensory processing. Specifically, we will examine the hypothesis that short-latency non-lemniscal inputs onto L6 regulate cortical sound processing in a timing-dependent manner and control the tuning and temporal fidelity of sound responses. To achieve this goal, this project aims to (1) Delineate the anatomy of the fast non- lemniscal pathway from the cochlear nucleus to the auditory cortex using both anatomical tracing and in vivo unit recordings, (2) Determine the synaptic impact of the non-lemniscal input onto cortical cell types by performing targeted whole-cell recordings in cortical slices while simultaneously activating L6-targeting thalamic inputs, and (3) Identify the roles of the fast non-lemniscal input in cortical sound processing in vivo by optogenetically manipulating thalamic inputs onto L6 during unit recordings in the mice performing sound- guided behaviors. Through our research, we seek to provide a more holistic understanding of auditory processing across the two major ascending pathways. Since parallel thalamocortical inputs onto L4 and L6 are conserved across sensory modalities, results from this project will provide insights into the generalizable principles underlying the cortical circuitry of sensory integration. Ultimately, these studies will help the future development of targeted treatments for not only hearing disorders but also other sensory integration dysfunctions.

项目总结