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：主要感觉皮层分析感官信息并存储有关学习感觉的信息经验。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神经元的调整特性依赖于活动更改。这种皮质图可塑性被认为是听觉记忆的基材通过促进对行为重要的音调的反应。在少年动物中，皮质图可塑性 ACX可以通过一定声音的被动环境富集来诱导。在啮齿动物中，少年皮质 MAP可塑性仅限于几天（即关键时期早期）。在成熟的动物中，皮质图只有当调节在行为上很重要或与调制的激活配对时，才能诱导可塑性（例如胆碱能，多巴胺能，去甲肾上腺素能）预测。在上一个资金期间，我们确定皮质图可塑性由与长期增强（LTP）和长期相同的机制编码丘脑皮质（TC）兴奋性突触的抑郁症（LTD）。 TC投影是主要的感官输入新皮层并有助于形成皮质图。在大脑切片中，我们证明了TC突触关键时期早期后不会损失可塑性，而是获得了可以释放的门控机制通过在突触前末端激活胆碱能受体。释放门控后，LTP/LTD在TC突触体内的皮质图可塑性发生在关键早期早期的动物中。腺苷机械，由产生腺苷的Ecto-5'-核苷酸酶（NT5E）和A1腺苷受体（A1RS）组成门控。如果声学刺激与中断配对，则可以在成年人中重新建立少年可塑性听觉丘脑中的NT5E或A1R信号传导。这种可塑性发生在皮质图和单个ACX中醒着成年小鼠的神经元与长期歧视能力的长期改善有关。在这种竞争性更新，我们建议测试丘脑中腺苷机制的假设在ACX地图期间，将信息从调制预测传输到丘脑的主中调解人成人的可塑性。在AIM 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在激活或停用门控机制的同时，调节性预测。在AIM 2中，我们将探索通过研究腺苷的年龄依赖性来终止关键时期的分子机制生产。在AIM 3中，我们将确定门控机制的时间尺度。使用快速扫描循环伏安法在清醒老鼠中，我们发现腺苷在听觉丘脑中瞬时释放响应声音的皮层。我们建议阐明这种声音诱发的机制和动力学关键早期之前和之后的腺苷释放，并确定其如何影响丘脑的峰值声音刺激过程中继电器和皮质神经元。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的基础。