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Synaptic mechanisms of auditory memory

听觉记忆的突触机制

基本信息

批准号：
8847316
负责人：
Stanislav S Zakharenko
金额：
$ 36.82万
依托单位：
ST. JUDE CHILDREN'S RESEARCH HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-07-01 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8847316
关键词：
Acoustics Adenosine Affect Animals Auditory Auditory area Auditory system Basal Nucleus of Meynert Behavioral Cerebral cortex Cholinergic Receptors Development Disinhibition Environment Evaluation Excitatory Synapse Frequencies Future Glutamates Government Health Image In Vitro Knowledge Laser Scanning Microscopy Learning Life Long-Term Depression Long-Term Potentiation Maps Measures Memory Molecular Mus Mutant Strains Mice Neocortex Neonatal Neurons Organism Perceptual learning Persons Presynaptic Terminals Process Production Property Rodent Role Saint Jude Children&apos s Research Hospital Sensory Signal Transduction Slice Source Stimulus Synapses Synaptic plasticity Testing Thalamic structure Training Whole-Cell Recordings aged base cholinergic cortex mapping critical period environmental enrichment for laboratory animals experience in vivo juvenile animal mature animal novel optogenetics postnatal postsynaptic presynaptic pup research study response sensory cortex sensory input sound sound frequency synaptic function tool two-photon

项目摘要

DESCRIPTION (provided by applicant): Primary sensory cortices not only analyze sensory information but also store information about learned sensory experiences. The auditory cortex (ACx) acquires and retains specific memory traces about the behavioral significance of selected sounds. During learning, the tuning properties of ACx neurons undergo activity-dependent changes. This cortical map plasticity, which is believed to be a substrate of auditory memory, is characterized by the facilitation of responses to behaviorally important tones at the expense of other frequencies. In mature animals, it can be induced by pairing selected tones with activation of cholinergic projections from the nucleus basalis. In young animals, cortical map plasticity in the ACx can be induced by passive enrichment of the environment with a certain sound. Cellular mechanisms of cortical map plasticity are unknown. In this project, we will test our hypothesis that bidirectional changes in cortical responses during learning can be encoded by synaptic mechanisms such as long-term potentiation (LTP) and long-term depression (LTD) at thalamocortical (TC) excitatory synapses.TC projections provide the major ascending sensory input to the neocortex and contribute to the formation of cortical maps in sensory cortices. Thus, synaptic plasticity at TC synapses should greatly influence cortical map plasticity in the ACx. However, it has been postulated that LTP and LTD at TC synapses are limited to the early postnatal period that in rodents corresponds to the first several postnatal days. This suggests that TC synaptic plasticity cannot be a substrate of cortical map plasticity and perceptual memory in mature animals. Recently, we showed that TC synaptic plasticity is not lost in the mature ACx; instead, it acquires gating mechanisms during postnatal development that can be released by activating cholinergic receptors on presynaptic terminals of TC projections. Once gating is released, LTP and LTD can occur at TC synapses of animals aged far beyond the early critical period. Using 2-photon imaging of synaptic function, 2-photon glutamate uncaging, and whole-cell recordings in TC slices from mature animals, we recently identified novel cellular and molecular mechanisms of LTD and LTP at TC synapses. We also began characterizing the gating mechanisms. Here, we propose to test our hypothesis that TC synaptic plasticity underlies cortical map plasticity in mature animals. Using electrophysiologic mapping in vivo, we will determine whether mechanisms that affect LTP and LTD at TC synapses also affect cortical map plasticity in the ACx. Using imaging and optogenetic, molecular, and electrophysiological tools, we will further characterize the mechanisms of TC synaptic plasticity. Identifying these mechanisms will expand our understanding of cortical map plasticity in the ACx. Knowledge gained from these studies will provide the basis for future elucidation of the cellular and molecular mechanisms of auditory memory.

描述（申请人提供）：初级感觉皮层不仅分析感觉信息，还存储有关学习到的感觉经验的信息。听觉皮层（ACx）获得并保留有关所选声音的行为意义的特定记忆痕迹。在学习过程中，ACx神经元的调谐特性经历活动依赖性变化。这种皮层地图可塑性被认为是听觉记忆的基础，其特征在于以牺牲其他频率为代价来促进对行为上重要的音调的反应。在成年动物中，它可以通过激活基底核的胆碱能投射与选定的音调配对来诱导。在年轻的动物中，ACx的皮质地图可塑性可以通过被动丰富的环境与一定的声音来诱导。皮质地图可塑性的细胞机制尚不清楚。在本研究中，我们将验证我们的假设，即学习过程中皮层反应的双向变化可以通过突触机制编码，如丘脑皮层（TC）兴奋性突触的长时程增强（LTP）和长时程抑制（LTD），TC投射提供了主要的向上感觉输入到新皮层，并有助于感觉皮层中皮层地图的形成。因此，在TC突触的突触可塑性应大大影响皮质地图可塑性的ACx。然而，它已被假定，LTP和LTD在TC突触仅限于出生后的早期，在啮齿类动物中对应于出生后的前几天。这表明TC突触可塑性不能成为成熟动物皮层地图可塑性和知觉记忆的底物。最近，我们发现，TC突触可塑性并没有失去在成熟的ACx，相反，它获得门控机制，在出生后的发展，可以通过激活胆碱能受体突触前终端的TC预测释放。一旦门控被释放，LTP和LTD可以发生在年龄远远超过早期关键期的动物的TC突触。使用2-光子成像的突触功能，2-光子谷氨酸uncaging，和全细胞记录在TC切片从成熟的动物，我们最近确定了新的细胞和分子机制的LTD和LTP在TC突触。我们也开始描述门控机制。在这里，我们建议测试我们的假设，TC突触可塑性的基础上皮质地图可塑性在成熟的动物。使用电生理标测在体内，我们将确定是否机制，影响LTP和LTD在TC突触也影响皮质地图可塑性的ACx。利用影像学和光遗传学、分子学和电生理学工具，我们将进一步描述TC突触可塑性的机制。确定这些机制将扩大我们的理解皮层地图可塑性的ACx。从这些研究中获得的知识将为未来阐明听觉记忆的细胞和分子机制提供基础。