Synaptic, Cellular and Circuit Mechanisms of Cortical Plasticity after Cochlear Damage
耳蜗损伤后皮质可塑性的突触、细胞和电路机制
基本信息
- 批准号:10273218
- 负责人:
- 金额:$ 61.92万
- 依托单位:
- 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:2021-06-03 至 2026-05-31
- 项目状态:未结题
- 来源:
- 关键词:Acoustic NerveAreaAuditoryAuditory PerceptionAuditory areaAuditory systemBiophysicsBrainBrain StemCellsCochleaCommunicationComplexConsciousDetectionDevelopmentDiscriminationDiseaseElectrophysiology (science)EquilibriumEsthesiaExhibitsHealthHyperacusisIn VitroInterneuronsIon ChannelKnowledgeMediatingMissionMusNeuronsNoise-Induced Hearing LossOrganPain ResearchParvalbuminsPathway interactionsPerceptionPeripheralPharmacologyPharmacotherapyPropertyPyramidal TractsRecoveryResearchRoleSchizophreniaSensorySomatostatinSynapsesSystemTestingThalamic structureTimeTinnitusUnited States National Institutes of HealthVasoactive Intestinal Peptideauditory thalamusawakebasecell typedisabilityhearing impairmentimaging studyimprovedin vivoin vivo two-photon imagingnovelpainful neuropathyprogramsrehabilitation paradigmsensory cortexsensory systemsoundtwo photon microscopy
项目摘要
PROJECT SUMMARY
In all sensory systems, peripheral sensory organ damage leads to compensatory cortical plasticity that supports
a remarkable recovery of perceptual capabilities. In the auditory system, while auditory nerve input to the
brainstem is significantly reduced after cochlear damage, sound-evoked cortical activity is maintained or even
enhanced. This recovery is due to increased cortical sensitivity (gain) to the spared auditory input. Although this
plasticity does not support features of sound processing encoded by the precise timing of neuronal firing, such
as complex sound discrimination, it provides a remarkable recovery of sound detection. A major gap in
knowledge is the lack of a precise mechanism that explains how this plasticity is implemented and distributed
over the diverse excitatory and inhibitory cortical neurons, synapses and circuits. Here we propose a strategic,
cooperative, time-dependent, cell type- and synapse-specific plasticity program that restores cortical sound
processing. The results from our studies will advance the field to a new level of understanding regarding cortical
plasticity after peripheral organ damage, and will inspire the development of well-timed, cell-specific treatments
and rehabilitative paradigms and cures that may further enhance the recovery of perception after hearing loss,
and mitigate the development of brain plasticity-related disorders, such as hyperacusis and tinnitus.
Cortical principal neurons (PN) and interneurons (IN) are very diverse and thus capable of supporting a
coordinated and collaborative plan for achieving cortical recovery. The major classes of cortical neurons include
vasoactive intestinal-peptide (VIP), somatostatin (SOM) and parvalbumin (PV) expressing IN sub-classes, as
well as intratelencephalic (IT), layer (L) 5 pyramidal tract (PT), and L6 corticothalamic (CT) PNs. Based on our
preliminary results, we propose that: 1) PVs are the network “stabilizers”; 2) VIPs are the “enablers” that regulate
SOM activity; and 3) SOMs are the “modulators” that allow for high PN gain. At the cellular and synaptic level,
we propose that soon after cochlear damage: 4) PVs and PTs exhibit a decrease in intrinsic excitability; 5) CTs
exhibit an increase in intrinsic excitability; and 6) thalamic synaptic input to deep cortical layers is shifted from
CT/PT equivalent to CT dominant. Overall, our proposed research and hypotheses provide an experimental
platform to probe how multiple cortical neuronal sub-classes restore cortical processing after peripheral input
loss (Aims 1 and 3). In combination with Aims 2 and 3, our proposed studies will determine the underlying intrinsic
(Aim 2) and synaptic mechanisms (Aim 3) that mediate this plasticity.
项目总结
在所有感觉系统中,外周感觉器官损伤会导致代偿性皮质可塑性,从而支持
感知能力的显著恢复。在听觉系统中,当听神经输入到
耳蜗损伤后脑干明显减少,声诱发皮层活动维持甚至维持
增强版。这种恢复是由于皮层对备用听觉输入的敏感度(增益)增加。虽然这件事
可塑性不支持由神经元放电的精确定时编码的声音处理功能,例如
作为复杂的声音识别,它提供了显著的声音检测恢复。在以下方面存在重大差距
知识缺乏一种精确的机制来解释这种可塑性是如何实现和分配的
在不同的兴奋性和抑制性皮质神经元、突触和回路上。在这里,我们提出了一个战略性的,
恢复皮质声音的合作性、时间依赖性、细胞类型和突触特定的可塑性程序
正在处理。我们的研究结果将推动该领域对大脑皮层的理解达到一个新的水平
外周器官损伤后的可塑性,并将激励适时、细胞特异性治疗的发展
以及可以进一步促进听力损失后感知恢复的康复范例和治疗方法,
并减轻与大脑可塑性相关的疾病的发展,如听力过敏症和耳鸣。
皮质主神经元(PN)和中间神经元(IN)是非常多样化的,因此能够支持
协调和协作的计划,以实现皮质恢复。皮质神经元的主要类别包括
血管活性肠肽(VIP)、生长抑素(SOM)和小白蛋白(PV)亚类表达,AS
脑内(IT)、层(L)、5锥体束(PT)和L6皮质丘脑(CT)PNS。基于我们的
初步研究结果表明:1)VP是网络的“稳定器”;2)VIP是网络调节的“使能器”
SOM活性;3)SOM是允许高Pn增益的“调节器”。在细胞和突触水平上,
我们提出耳蜗病后不久:4)PV和PTS表现出内在兴奋性的降低;5)CTS
表现出内在兴奋性的增加;以及6)丘脑向皮质深层的突触输入从
CT/PT相当于CT占优势。总体而言,我们提出的研究和假设提供了一个实验性的
探索多个皮质神经元亚类如何在外周输入后恢复皮质处理的平台
损失(目标1和3)。结合目标2和目标3,我们提议的研究将确定潜在的内在
(目标2)和调节这种可塑性的突触机制(目标3)。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Thanos Tzounopoulos其他文献
Thanos Tzounopoulos的其他文献
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{{ truncateString('Thanos Tzounopoulos', 18)}}的其他基金
Cortical neuromodulatory mechanisms underlying adaptation and plasticity
适应和可塑性的皮质神经调节机制
- 批准号:
10794638 - 财政年份:2023
- 资助金额:
$ 61.92万 - 项目类别:
Synaptic, Cellular and Circuit Mechanisms of Cortical Plasticity after Cochlear Damage
耳蜗损伤后皮质可塑性的突触、细胞和电路机制
- 批准号:
10623300 - 财政年份:2021
- 资助金额:
$ 61.92万 - 项目类别:
Synaptic, Cellular and Circuit Mechanisms of Cortical Plasticity after Cochlear Damage
耳蜗损伤后皮质可塑性的突触、细胞和电路机制
- 批准号:
10416074 - 财政年份:2021
- 资助金额:
$ 61.92万 - 项目类别:
Cell-specific Synaptic Plasticity in the Auditory Brainstem
听觉脑干中的细胞特异性突触可塑性
- 批准号:
7857728 - 财政年份:2009
- 资助金额:
$ 61.92万 - 项目类别:
Cell-specific Synaptic Plasticity in the Auditory Brainstem
听觉脑干中的细胞特异性突触可塑性
- 批准号:
9236791 - 财政年份:2007
- 资助金额:
$ 61.92万 - 项目类别:
Cell-specific Synaptic Plasticity in the Auditory Brainstem
听觉脑干中的细胞特异性突触可塑性
- 批准号:
7759859 - 财政年份:2007
- 资助金额:
$ 61.92万 - 项目类别:
Cell-specific Synaptic Plasticity in the Auditory Brainstem
听觉脑干中的细胞特异性突触可塑性
- 批准号:
8429374 - 财政年份:2007
- 资助金额:
$ 61.92万 - 项目类别:
Cell-specific Synaptic Plasticity in the Auditory Brainstem
听觉脑干中的细胞特异性突触可塑性
- 批准号:
8609018 - 财政年份:2007
- 资助金额:
$ 61.92万 - 项目类别:
Cell-specific Synaptic Plasticity in the Auditory Brainstem
听觉脑干中的细胞特异性突触可塑性
- 批准号:
7755033 - 财政年份:2007
- 资助金额:
$ 61.92万 - 项目类别:
Cell-specific Synaptic Plasticity in the Auditory Brainstem
听觉脑干中的细胞特异性突触可塑性
- 批准号:
7258254 - 财政年份:2007
- 资助金额:
$ 61.92万 - 项目类别:
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