Synaptic mechanisms of auditory memory

听觉记忆的突触机制

• 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
• 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' 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

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）：初级感觉皮层不仅分析感觉信息，还存储有关习得的感觉体验的信息。听觉皮层 (ACx) 获取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 神经元的调节特性会发生依赖于活动的变化。这种皮质图可塑性被认为是听觉记忆的基础，其特点是以牺牲其他频率为代价，促进对行为重要音调的反应。在成熟动物中，它可以通过将选定的音调与基底核胆碱能投射的激活配对来诱导。在幼年动物中，ACx 中的皮质图可塑性可以通过被动丰富特定声音的环境来诱导。皮质图可塑性的细胞机制尚不清楚。在这个项目中，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由突触机制编码，例如丘脑皮质 (TC) 兴奋性突触的长期增强 (LTP) 和长期抑制 (LTD)。TC 预测为新皮质提供主要的上升感觉输入，并有助于感觉皮质中皮质图的形成。因此，TC 突触的突触可塑性应该极大地影响 ACx 的皮质图可塑性。然而，据推测，TC 突触处的 LTP 和 LTD 仅限于出生后早期，即啮齿类动物对应的出生后最初几天。这表明 TC 突触可塑性不能成为成熟动物皮质图可塑性和知觉记忆的基础。最近，我们发现成熟的 ACx 中 TC 突触可塑性并未丧失；相反，它在出生后发育过程中获得了门控机制，可以通过激活 TC 投射突触前末端的胆碱能受体来释放。一旦门控被释放，LTP 和 LTD 可能会发生在年龄远远超过早期关键期的动物的 TC 突触处。利用突触功能的 2 光子成像、2 光子谷氨酸解禁和成熟动物 TC 切片的全细胞记录，我们最近确定了 TC 突触中 LTD 和 LTP 的新细胞和分子机制。我们还开始表征门控机制。在这里，我们建议检验我们的假设，即 TC 突触可塑性是成熟动物皮质图可塑性的基础。使用体内电生理图，我们将确定影响 TC 突触 LTP 和 LTD 的机制是否也会影响 ACx 中的皮质图可塑性。利用成像和光遗传学、分子和电生理学工具，我们将进一步表征 TC 突触可塑性的机制。识别这些机制将扩大我们对 ACx 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。