Corticofugal Circuits for Active Listening
积极倾听的皮质回路
基本信息
- 批准号:10668486
- 负责人:
- 金额:$ 70.34万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-03-01 至 2027-07-31
- 项目状态:未结题
- 来源:
- 关键词:AcetylcholineActive ListeningAcuteAmygdaloid structureAnimalsArousalAssociation LearningAuditoryAuditory PerceptionAuditory areaAwardAwarenessAxonBasal Nucleus of MeynertBehaviorBehavioralBrainCalciumCell NucleusCholinergic ReceptorsCodeCorpus striatum structureCouplingDementiaDesire for foodDetectionDiagonal Band NucleusEquilibriumFailureFiberGeneticHearingHippocampusImageLearningMeasuresMedialMedial geniculate bodyMediatingMemoryModalityModelingMonitorMusNeocortexNeurodegenerative DisordersNeuronsOperant ConditioningOutputPhasePreparationPresynaptic TerminalsPropertyProsencephalonPsychological reinforcementPublishingPupilRehabilitation therapyReportingResearchRoleSensorySensory DisordersSliceStimulusSynaptic plasticityTailTestingThalamic structureTransgenic MiceWhole-Cell RecordingsWorkantagonistauditory nucleiauditory stimulusaversive conditioningawakebasal forebrainbasal forebrain cholinergic neuronsbasecell typecholinergiccholinergic neuronconditioningindexingmemory consolidationneocorticalneuralnovel strategiesnovel therapeuticsoptogeneticspermissivenessreceptive fieldresponsesensorsoundtwo-photon
项目摘要
Cholinergic basal forebrain (CBF) neurons project throughout the neocortex, hippocampus, and amygdala to
modulate perceptual salience and regulate synaptic plasticity underlying learning and memory. CBF research
has focused on rostral regions, including the medial septum, nuclei of the diagonal band, and nucleus basalis
(NB). The caudal extreme of the basal forebrain has been largely overlooked, yet our research suggests that
this caudal tail region – much like the tail of the striatum – can be conceptualized as a distinct functional
subdomain with categorically different response properties than more rostral regions. The projections of CBF
tail neurons (CBFt) are concentrated in two regions: the auditory cortex (ACtx) and the thalamic reticular
nucleus (TRN). Our published and preliminary recordings from CBFt neurons in passively listening mice reveal
surprisingly strong, short-latency, low-threshold responses to a broad class of auditory stimuli that have no
explicit behavioral relevance. Comparable responses are not observed for stimuli in other modalities or from
more rostral CBF neurons. CBFt sound responses are not stable, but instead are rapidly and selectively
enhanced for threat-predicting sounds during Pavlovian and instrumental learning paradigms. Thus, our
studies of the tail region suggest a different model for cholinergic modulation of cortical sound processing in
which the ACtx is continuously bombarded by sound-triggered acetylcholine (ACh) surges that reorganize
during learning to highlight relevant sounds and guide cortical receptive field plasticity. Here, we describe three
specific aims for the coming project period that will illuminate how the CBFt regulates thalamocortical sound
processing, perceptual awareness of sound, and associative plasticity during auditory learning. Studies in Aim
1 will test an inverted-U hypothesis for cholinergic modulation of sound processing, which holds that sensory
tuning in the primary ACtx (A1) and TRN become imprecise and unreliable during transient peaks and troughs
of local endogenous ACh release. Further, we predict that these effects can be accounted for – in part – by the
particularly strong influence of CBFt-mediated ACh release on A1 layer 6 corticothalamic neurons, as tested by
studies in both intact and acute thalamocortical brain slice preparations. Aim 2 will extend these ideas to the
behavioral domain by showing that occasional lapses in thalamocortical encoding and perceptual awareness of
target sounds (i.e., miss trials) can be attributed to stochastic peaks and troughs in CBFt-mediated ACh levels
immediately preceding target sound onset. Aim 3 will test the hypothesis that enhanced CBFt responses to
sounds associated with aversive – but not appetitive – reinforcement is sufficient to shift A1 sound
representations from a mode of net stability to heightened plasticity that supports associative auditory learning.
These hypotheses will be tested through the combined application of genetically encoded ACh sensor imaging,
optogenetics, multi-regional single unit recordings, and 2-photon calcium imaging of CBFt or NB axons in
awake transgenic mice during voluntary and involuntary behavioral reporting of sound perception.
胆碱能基底前脑(CBF)神经元投射到整个新皮层、海马和杏仁核,
调节知觉的显著性和调节学习和记忆基础的突触可塑性。CBF研究
主要集中在吻侧区域,包括内侧隔、斜角带核和基底核
(注)。基底前脑的尾端在很大程度上被忽视了,然而我们的研究表明,
这个尾部区域--很像纹状体的尾部--可以被概念化为一个独特的功能区,
子域与不同的反应性质比更多的吻部地区。CBF的预测
尾神经元(CBFt)集中在两个区域:听觉皮层(ACtx)和丘脑网状
核(TRN)。我们发表的和初步的记录来自被动倾听小鼠的CBFt神经元,
令人惊讶的是,对一大类听觉刺激的短潜伏期低阈值反应,
外显行为相关性对于其他方式的刺激或来自
更多的嘴侧CBF神经元。CBFt声音反应并不稳定,而是快速和选择性的
在巴甫洛夫和工具学习范式中,威胁预测声音的能力得到了增强。所以我们
对尾区的研究表明,大脑皮层声音处理的胆碱能调制是一种不同的模型,
ACtx不断受到声音触发的乙酰胆碱(ACh)激增的轰击,
在学习过程中,突出相关的声音和指导皮层感受野可塑性。在这里,我们描述了三个
下一个项目期间的具体目标,将阐明CBFt如何调节丘脑皮质音
处理,知觉意识的声音,和联想可塑性在听觉学习。研究目的
1将测试一个倒U型假说的胆碱能调制的声音处理,这认为,感觉
在瞬时波峰和波谷期间,初级ACtx(A1)和TRN的调谐变得不精确且不可靠
局部内源性乙酰胆碱释放。此外,我们预测,这些影响可以解释-部分-由
CBFt介导的ACh释放对A1层6皮质丘脑神经元的影响特别强烈,如通过
对完整和急性丘脑皮质脑切片制备物的研究。目标2将把这些想法扩展到
行为领域的研究表明,丘脑皮质编码和知觉意识的偶尔失误,
目标声音(即,缺失试验)可归因于CBFt介导的ACh水平的随机峰和谷
就在目标声音开始之前。目的3将检验增强CBFt对
与厌恶相关的声音-但不是食欲-强化足以转移A1声音
从网络稳定性模式到支持联想听觉学习的增强可塑性。
这些假设将通过基因编码的乙酰胆碱传感器成像的组合应用进行测试,
光遗传学、多区域单单位记录和CBFt或NB轴突的双光子钙成像,
清醒的转基因小鼠在自愿和非自愿的行为报告的声音感知。
项目成果
期刊论文数量(7)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
A functional topography within the cholinergic basal forebrain for encoding sensory cues and behavioral reinforcement outcomes.
- DOI:10.7554/elife.69514
- 发表时间:2021-11-25
- 期刊:
- 影响因子:7.7
- 作者:Robert B;Kimchi EY;Watanabe Y;Chakoma T;Jing M;Li Y;Polley DB
- 通讯作者:Polley DB
Inverted central auditory hierarchies for encoding local intervals and global temporal patterns.
- DOI:10.1016/j.cub.2021.01.076
- 发表时间:2021-04-26
- 期刊:
- 影响因子:0
- 作者:Asokan MM;Williamson RS;Hancock KE;Polley DB
- 通讯作者:Polley DB
Behavioral Approaches to Study Top-Down Influences on Active Listening.
- DOI:10.3389/fnins.2021.666627
- 发表时间:2021
- 期刊:
- 影响因子:4.3
- 作者:Clayton KK;Asokan MM;Watanabe Y;Hancock KE;Polley DB
- 通讯作者:Polley DB
Optimizing optogenetic stimulation protocols in auditory corticofugal neurons based on closed-loop spike feedback.
基于闭环尖峰反馈优化听觉皮质神经元的光遗传学刺激方案。
- DOI:10.1088/1741-2552/ab39cf
- 发表时间:2019
- 期刊:
- 影响因子:4
- 作者:Vila,Charles-Henri;Williamson,RossS;Hancock,KennethE;Polley,DanielB
- 通讯作者:Polley,DanielB
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Daniel B. Polley其他文献
Application of frequency modulated chirp stimuli for rapid and sensitive ABR measurements in the rat
应用调频啁啾刺激进行大鼠快速、灵敏的 ABR 测量
- DOI:
- 发表时间:
2008 - 期刊:
- 影响因子:2.8
- 作者:
C. Spankovich;Linda J. Hood;Linda J. Hood;D. Grantham;Daniel B. Polley;Daniel B. Polley - 通讯作者:
Daniel B. Polley
Daniel B. Polley的其他文献
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{{ truncateString('Daniel B. Polley', 18)}}的其他基金
Neural Pathophysiology and Suprathreshold Processing in Older Adults with Elevated Thresholds
阈值升高的老年人的神经病理生理学和阈上处理
- 批准号:
10222647 - 财政年份:2017
- 资助金额:
$ 70.34万 - 项目类别:
Maladaptive central plasticity and suprathreshold hearing disorders in humans with sensorineural hearing loss and their relation to biomarkers of cochlear synaptopathy
感音神经性听力损失患者的适应不良中枢可塑性和阈上听力障碍及其与耳蜗突触病生物标志物的关系
- 批准号:
10641781 - 财政年份:2017
- 资助金额:
$ 70.34万 - 项目类别:
A chemical-genetic approach to decipher the function of corticothalamic feedback
破译皮质丘脑反馈功能的化学遗传学方法
- 批准号:
8610288 - 财政年份:2013
- 资助金额:
$ 70.34万 - 项目类别:
A chemical-genetic approach to decipher the function of corticothalamic feedback
破译皮质丘脑反馈功能的化学遗传学方法
- 批准号:
8512439 - 财政年份:2013
- 资助金额:
$ 70.34万 - 项目类别:
Activity-Dependent Influences on Auditory Circuits
对听觉回路的活动依赖性影响
- 批准号:
8471096 - 财政年份:2009
- 资助金额:
$ 70.34万 - 项目类别:
Activity-Dependent Influences on Auditory Circuits
对听觉回路的活动依赖性影响
- 批准号:
10611996 - 财政年份:2009
- 资助金额:
$ 70.34万 - 项目类别:
Activity-Dependent Influences on Auditory Circuits
对听觉回路的活动依赖性影响
- 批准号:
10375528 - 财政年份:2009
- 资助金额:
$ 70.34万 - 项目类别:
The Auditory Phenotype of Kv Channel Gene Mutations
Kv通道基因突变的听觉表型
- 批准号:
7638898 - 财政年份:2009
- 资助金额:
$ 70.34万 - 项目类别:
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