Synaptic mechanisms of auditory memory

听觉记忆的突触机制

• 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
• 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' -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' 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

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建。 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。

项目成果

Rejuvenation of plasticity in the brain: opening the critical period.

大脑可塑性的复兴：开启关键期。

• 发表时间: 2019
• 影响因子: 5.7
• 作者: Patton, Mary H;Blundon, Jay A;Zakharenko, Stanislav S
• 通讯作者: Zakharenko, Stanislav S

MicroRNAs in the Onset of Schizophrenia.

MicroRNA 在精神分裂症发作中的作用。

• 发表时间: 2021-10-06
• 影响因子: 6
• 作者: Thomas, Kristen T;Zakharenko, Stanislav S
• 通讯作者: Zakharenko, Stanislav S

Schizophrenia-related microdeletion causes defective ciliary motility and brain ventricle enlargement via microRNA-dependent mechanisms in mice.

精神分裂症相关的微缺失通过 microRNA 依赖性机制导致小鼠纤毛运动缺陷和脑室扩大。

• 发表时间: 2020
• 影响因子: 16.6
• 作者: Eom, Tae;Han, Seung Baek;Kim, Jieun;Blundon, Jay A;Wang, Yong;Yu, Jing;Anderson, Kara;Kaminski, Damian B;Sakurada, Sadie Miki;Pruett;Horner, Linda;Wagner, Ben;Robinson, Camenzind G;Eicholtz, Matthew;Rose, Derek C
• 通讯作者: Rose, Derek C

Forward suppression in the auditory cortex is caused by the Ca(v)3.1 calcium channel-mediated switch from bursting to tonic firing at thalamocortical projections.

听觉皮层的前向抑制是由 Ca(v)3.1 钙通道介导的丘脑皮层投射从突发放电到强直放电的转换引起的。

• 发表时间: 2013-11-27
• 作者: Bayazitov, Ildar T;Westmoreland, Joby J;Zakharenko, Stanislav S
• 通讯作者: Zakharenko, Stanislav S

Sound-evoked adenosine release in cooperation with neuromodulatory circuits permits auditory cortical plasticity and perceptual learning.

声音诱发的腺苷释放与神经调节回路配合，可实现听觉皮层可塑性和知觉学习。

• 发表时间: 2024-02-27
• 影响因子: 8.8
• 作者: Bayazitov, Ildar T;Teubner, Brett J W;Feng, Feng;Wu, Zhaofa;Li, Yulong;Blundon, Jay A;Zakharenko, Stanislav S
• 通讯作者: Zakharenko, Stanislav S