Synaptic mechanisms of auditory memory

听觉记忆的突触机制

基本信息

批准号：
8576425
负责人：
Stanislav S Zakharenko
金额：
$ 37.19万
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 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8576425
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 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 Photons 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 critical period environmental enrichment for laboratory animals experience in vivo juvenile animal mature animal novel optogenetics postnatal postsynaptic presynaptic public health relevance pup research study response sensory cortex sound sound frequency synaptic function tool

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（由申请人提供）：主要感觉皮层不仅分析感官信息，还可以存储有关学习的感官体验的信息。听觉皮层（ACX）获取并保留有关所选声音行为意义的特定记忆痕迹。在学习过程中，ACX神经元的调整特性会经历活动依赖性变化。这种皮质图可塑性被认为是听觉记忆的基板，其特征是促进对行为重要的音调的响应，但以其他频率为代价。在成熟的动物中，可以通过将选定的音调与基底细胞核的胆碱能投影相配对来诱导。在幼小的动物中，ACX中的皮质图可塑性可以通过具有一定声音的环境富集来诱导。皮质图塑性的细胞机制尚不清楚。在该项目中，我们将测试我们的假设，即学习过程中皮质反应的双向变化可以通过突触机制来编码，例如长期增强（LTP）和丘脑皮层（TC）兴奋性突触的长期抑郁（LTD）。TC投影提供了对Neocortex的主要升级感官和撰写的序列，并为Neocorts撰写了主要的升级感。因此，TC突触时的突触可塑性应极大地影响ACX中的皮质图可塑性。但是，已经假定，TC突触的LTP和LTD仅限于啮齿动物中早期的早期，该时期对应于前几天的前几天。这表明TC突触可塑性不能是成熟动物中皮质图可塑性和感知记忆的底物。最近，我们表明TC突触可塑性在成熟的ACX中不会丧失。取而代之的是，它在产后发育过程中获得了门控机制，该机制可以通过在TC投影的突触前末端激活胆碱能受体来释放。一旦释放门控，LTP和LTD可能会发生在年龄远远超出关键时期早期的动物的TC突触中。使用突触功能的2光子成像，2光片谷氨酸渗透以及成熟动物的TC切片中的全细胞记录，我们最近在TC突触中确定了LTD和LTP的新型细胞和分子机制。我们还开始表征门控机制。在这里，我们建议测试我们的假设，即TC突触可塑性是成熟动物中皮质图可塑性的基础。使用体内电生理图映射，我们将确定影响LTP和LTD在TC突触时的机制是否还会影响ACX中的皮质图可塑性。使用成像和光遗传学，分子和电生理工具，我们将进一步表征TC突触可塑性的机制。确定这些机制将扩大我们对ACX中皮质图可塑性的理解。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。