权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Synaptic mechanisms of auditory memory

听觉记忆的突触机制

基本信息

批准号：
10467043
负责人：
Stanislav S Zakharenko
金额：
$ 46.05万
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 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10467043
关键词：
5&apos -Nucleotidase Acoustic Stimulation Acoustics Adenosine Adenosine A1 Receptor Adolescent Adult Affect Age Agonist Animals Auditory Auditory area Auditory system Basal Nucleus of Meynert Behavioral Brain Cerebral cortex Cholinergic Receptors Data Dependence Development Discrimination Evaluation Excitatory Synapse Frequencies Funding Future Glutamates Government Individual Kinetics Knock-out Knowledge Language Development Learning Life Long-Term Depression Long-Term Potentiation Maps Mediating Mediator of activation protein Memory Molecular Mus Muscarinic Acetylcholine Receptor Mutant Strains Mice Neocortex Neuromodulator Neurons Organism Perceptual learning Periodicity Persons Presynaptic Terminals Production Property Purinergic P1 Receptors Receptor Activation Receptor Signaling Regulation Rodent Saint Jude Children&apos s Research Hospital Scanning Sensory Signal Transduction Slice Source Stimulus Synapses Synaptic plasticity Testing Thalamic structure Time Training Up-Regulation age related aged auditory thalamus awake cholinergic cortex mapping critical period environmental enrichment for laboratory animals experience experimental study in vivo juvenile animal mature animal mutant neural circuit noradrenergic novel optogenetics overexpression paired stimuli postnatal presynaptic prevent pup response sensory cortex sensory input sound sound frequency

项目摘要

Abstract: Primary sensory cortices analyze sensory information and store information about learned sensory experiences. The auditory cortex (ACx) acquires and retains 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. In juvenile animals, cortical map plasticity in the ACx can be induced by passive environmental enrichment with a certain sound. In rodents, juvenile cortical map plasticity is limited to a few postnatal days (i.e., the early critical period). In mature animals, cortical map plasticity can be induced only if tones are behaviorally important or paired with the activation of modulatory (e.g., cholinergic, dopaminergic, noradrenergic) projections. During the previous funding period, we determined that cortical map plasticity is encoded by the same mechanisms as long-term potentiation (LTP) and long-term depression (LTD) at thalamocortical (TC) excitatory synapses. TC projections are the major sensory input to the neocortex and contribute to the formation of cortical maps. In brain slices, we showed that TC synaptic plasticity is not lost after the early critical period, instead a gating mechanism is acquired that can be released by activating cholinergic receptors on presynaptic terminals. Once gating is released, LTP/LTD at TC synapses and cortical map plasticity in vivo occur in animals aged beyond the early critical period. Adenosine machinery, consisting of adenosine-producing ecto-5'-nucleotidase (Nt5e) and A1 adenosine receptors (A1Rs), provides the gating. Juvenile plasticity can be reestablished in adults, if acoustic stimuli are paired with disruption of Nt5e or A1R signaling in the auditory thalamus. This plasticity occurs in cortical maps and individual ACx neurons of awake adult mice and is associated with long-term improvement in tone-discrimination abilities. In this competitive renewal, we propose to test our hypothesis that the adenosine machinery in the thalamus is the master mediator that transmits information from modulatory projections to the thalamus during ACx map plasticity in adults. In Aim 1, we will induce cortical map plasticity in adults by pairing sounds with activation of modulatory projections while activating or deactivating the gating mechanism. In Aim 2, we will explore the molecular mechanisms of terminating the early critical period by investigating age dependency of adenosine production. In Aim 3, we will determine time scales of the gating mechanisms. Using fast-scan cyclic voltammetry in awake mice, we found that adenosine is transiently released in the auditory thalamus and cortex in response to sound. We propose to elucidate the mechanisms and kinetics of this sound-evoked adenosine release before and after the early critical period and determine how it affects spiking in thalamic relay and cortical neurons during sound stimulation. Knowledge gained from these studies will provide the basis for future elucidation of the cellular and molecular mechanisms of auditory memory.

摘要：初级感觉皮层分析感觉信息并存储有关习得感觉的信息经验。听觉皮层 (ACx) 获取并保留有关行为意义的记忆痕迹选定的声音。在学习过程中，ACx 神经元的调节特性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础，其特征是通过促进对行为上重要的语气的反应。在幼年动物中，皮质图可塑性 ACx 可以通过具有一定声音的被动环境富集来诱发。在啮齿动物中，幼年皮质地图可塑性仅限于出生后几天（即早期关键期）。在成熟动物中，皮质图只有当音调在行为上很重要或与调节的激活相结合时，才可以诱导可塑性（例如胆碱能、多巴胺能、去甲肾上腺素能）预测。在上一个资助期间，我们确定皮质图可塑性的编码机制与长时程增强（LTP）和长时程相同丘脑皮质 (TC) 兴奋性突触的抑制 (LTD)。 TC 预测是主要的感官输入新皮质并有助于皮质图的形成。在脑切片中，我们发现 TC 突触早期关键期过后，可塑性并没有丧失，而是获得了可以释放的门控机制通过激活突触前末端的胆碱能受体。一旦门控被释放，TC 突触处的 LTP/LTD 体内皮质图可塑性发生在年龄超过早期关键期的动物中。腺苷机械，由产生腺苷的 5'-核苷酸酶 (Nt5e) 和 A1 腺苷受体 (A1Rs) 组成，提供门控。如果声音刺激与破坏相结合，青少年的可塑性可以在成人中重新建立。听觉丘脑中的 Nt5e 或 A1R 信号传导。这种可塑性发生在皮质图和个体 ACx 中清醒成年小鼠的神经元，与音调辨别能力的长期改善有关。在这种竞争性更新，我们建议检验我们的假设，即丘脑中的腺苷机器是在 ACx 映射期间将信息从调制投影传输到丘脑的主中介器成人的可塑性。在目标 1 中，我们将通过将声音与激活配对来诱导成人的皮质图可塑性激活或停用门控机制时的调节投影。在目标 2 中，我们将探索通过研究腺苷的年龄依赖性终止早期关键期的分子机制生产。在目标 3 中，我们将确定门控机制的时间尺度。使用快速扫描循环对清醒小鼠进行伏安法分析，我们发现腺苷在听觉丘脑中短暂释放，皮层对声音的反应。我们建议阐明这种声音诱发的机制和动力学早期关键期之前和之后的腺苷释放，并确定它如何影响丘脑的尖峰声音刺激期间的中继和皮质神经元。从这些研究中获得的知识将提供为未来阐明听觉记忆的细胞和分子机制奠定基础。