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Dendritic Mechanisms Underlying Behaviorally-Relevant Activity in a Descending Auditory Pathway

下降听觉通路中行为相关活动的树突机制

基本信息

批准号：
10540726
负责人：
Pierre F Apostolides
金额：
$ 47.65万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-01-01 至 2025-12-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10540726
关键词：
Acoustics Active Listening Address Anatomy Anesthesia procedures Animals Apical Auditory Auditory area Auditory system Behavioral Behavioral Assay Biophysical Process Brain Brain Stem Cognition Cognitive Complex Data Dendrites Detection Discrimination Epidemic Event Feedback Frequencies Generations Glutamates Goals Head Hearing Hearing problem Image In Vitro Inferior Colliculus Knowledge Learning Light Linguistics Link Mediating Midbrain structure Mus Neurons Noise-Induced Hearing Loss Outcome Output Pathway interactions Perception Perceptual learning Play Presbycusis Public Health Quality of life Rewards Role Sensory Shapes Signal Transduction Speech Stimulus Stream Synapses Testing Time Tinnitus Work auditory discrimination auditory pathway auditory processing awake experience experimental study hearing impairment improved neuronal cell body novel strategies operation optogenetics physical property prevent segregation sensory system sound transmission process two-photon

项目摘要

Project Summary/Abstract Active listening is central to auditory cognition, supporting critical functions such as stream segregation, linguistic analysis and perceptual learning. To this end, the brain must accurately represent the physical properties of acoustic signals and subsequently parse sounds based on their behavioral relevance. Whereas the encoding of primary features such as amplitude and spectral content typically begins in specialized brainstem and midbrain circuits, the mechanisms by which sounds attain behavioral relevance are poorly understood. A long-standing assumption is that descending projections from auditory cortex, which contact most early ascending auditory circuits, play a critical role in ascribing behavioral relevance to sounds. Indeed, descending auditory cortical projections could provide an anatomical substrate for "top-down" signals to control the "bottom-up" encoding of acoustic features. Despite this presumed importance, little is known about the function of descending auditory cortical neurons in attentive listening, nor do we understand the biophysical mechanisms that dictate their contribution to central auditory processing. Our goal is to address these knowledge gaps in behaving mice by studying the descending pathway from auditory cortex to inferior colliculus, an auditory midbrain region critical for perceiving complex sounds. Our unpublished results support a working hypothesis whereby auditory cortico-collicular neurons encode learned information, thereby transmitting signals that amplify the representation of behaviorally relevant sound features in early auditory circuits. Our data further suggest that a key mechanism underlying the activity of auditory cortico-collicular neurons during active listening is the non-linear generation of dendritic spikes, powerful electrical events that initiate in the apical dendrites of cortical neurons and drive high-frequency burst firing at the soma. We propose testing these hypotheses using a unique combination of sub-cellular 2-photon Ca2+ imaging, optogenetics and behavioral assays in awake, head-fixed mice. The positive outcome will be to establish functional and mechanistic answers for the operation of a descending auditory cortical pathway during attentive listening, thereby shedding light on a critical yet poorly understood facet of the central auditory system.

项目总结/文摘