Understanding how activity drives diverse spine structural interactions

了解活动如何驱动不同的脊柱结构相互作用

• 批准号: 10840581
• 负责人: Inbal Israely
• 金额: $ 35.27万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10840581
• 关键词: Adult; Affect; Brain; Calcium; Chemosensitization; Complex; Dendritic Spines; Dependence; Development; Electrophysiology (science); Equilibrium; Event; Functional disorder; Glutamates; Goals; Growth; Hippocampus; Image; Individual; Information Storage; Learning; Logic; Long-Term Depression; Mediating; Mental Depression; Metabotropic Glutamate Receptors; Modification; Molecular; Monitor; Neuronal Dysfunction; Neurons; Outcome; Output; Pattern; Poisson Distribution; Process; Production; Protein Biosynthesis; Proteins; Publishing; Regulation; Resolution; Shapes; Signal Transduction; Slice; Specificity; Structure; Synapses; Synaptic plasticity; System; Testing; Vertebral column; Weight; Work; cognitive function; experience; experimental study; hippocampal pyramidal neuron; in vivo; information processing; interest; neural circuit; sensor; synaptic depression; two-photon

Abstract Brain circuits can be structurally rearranged with experience, and synaptic connections can grow and be eliminated, even in adults. We have shown that activity at specific inputs can lead to the production of new proteins, promoting either long lasting growth of single spines, or cooperation and competition between multiple synapses following potentiation. The balance between such interactions during structural plasticity can be the basis for plasticity at the circuit level, which allows for the rewiring of inputs within a dendritic domain. However, in order to be able to achieve such reorganization, mechanisms for strengthening co-active inputs as well as those that would achieve weakening and elimination of inputs would be required. The synthesis of new proteins is crucial for the long term storage of information, long lasting synaptic potentiation and structural plasticity. Of interest, this is also necessary for long lasting forms of synaptic depression, while much less is understood about the bidirectional regulation of structural plasticity. In addition to these Hebbian plasticity processes, additional forms of plasticity, such as homeostatic modulation, impact the plasticity capacity of dendritic branches. Homeostatic plasticity can scale synaptic currents, as well as spine structures, and can interact with Hebbian plasticity to elicit plasticity at non active neighbors. In addition, neurons receive diverse patterns of activity at their inputs, and it is unknown how these effect structural plasticity, or whether they are more or less likely to be subject to complex integration between co-active inputs. Therefore, using two-photon imaging and glutamate uncaging to stimulate and monitor plasticity at single spines or defined groups of spines, we will investigate the relationship between different forms of plasticity and spine structural changes. Specifically, we will determine whether synaptic depression can be induced at single inputs, what are the structural outputs of this form of plasticity, and whether protein synthesis dependent depression at multiple inputs can undergo competition. Further, we will investigate the structural plasticity rules of interactions between different forms of activity, such as Hebbian and homeostatic plasticity, when they coincide within a dendritic domain at multiple inputs. Beyond these forms of plasticity, we will also investigate non-regular patterns of activity, that follow instead a Poisson distribution, in order to build an understanding of how individual inputs process a diversity of activity, how they integrate this with events at co-active neighbors, and what are the structural correlates of these forms of plasticity. These experiments will allow us to investigate with unprecedented precision at the molecular, subcellular and circuit level the dynamics of synaptic interactions, and how they contribute to the building and refinement of neural circuits necessary for cognitive function.

抽象的 大脑回路可以根据经验在结构上重新排列，突触连接可以生长并变得更紧密。 甚至在成年人中也被消除了。我们已经证明，特定投入的活动可以导致新产品的生产 蛋白质，促进单个刺的长期持续生长，或多个刺之间的合作和竞争 增强后的突触。结构塑性过程中这种相互作用之间的平衡可以是 电路级可塑性的基础，允许在树突域内重新布线输入。然而， 为了能够实现这种重组，需要建立加强共同积极投入的机制以及 需要采取那些能够削弱和消除投入的措施。新蛋白质的合成 对于信息的长期存储、持久的突触增强和结构可塑性至关重要。的 有趣的是，这对于长期形式的突触抑制也是必要的，但人们对突触抑制的了解却少得多 结构塑性的双向调节。除了这些赫布塑性过程之外，还需要 可塑性的形式，例如稳态调节，会影响树突分支的可塑性能力。 稳态可塑性可以调节突触电流以及脊柱结构，并可以与 Hebbian 相互作用 可塑性以引发非活跃邻居的可塑性。此外，神经元在不同时间接收不同的活动模式 他们的输入，并且尚不清楚这些如何影响结构可塑性，或者它们是否或多或少有可能 受到协同输入之间复杂集成的影响。因此，使用双光子成像和谷氨酸 解开束缚以刺激和监测单个刺或特定刺组的可塑性，我们将研究 不同形式的可塑性与脊柱结构变化之间的关系。具体来说，我们将确定 是否可以通过单一输入诱发突触抑制，这种形式的结构输出是什么 可塑性，以及多种输入下蛋白质合成依赖性抑制是否可以进行竞争。 此外，我们将研究不同形式活动之间相互作用的结构可塑性规则，例如 作为赫布塑性和稳态可塑性，当它们在多个输入的树突域内重合时。超过 这些形式的可塑性，我们还将研究非常规的活动模式，而不是遵循泊松分布 分布，以便了解个体输入如何处理多样性的活动，它们如何 将其与共同活跃的邻居的事件相结合，以及这些可塑性形式的结构相关性是什么。 这些实验将使我们能够以前所未有的精度研究分子、亚细胞和 电路层面的突触相互作用的动态，以及它们如何有助于构建和完善 认知功能所必需的神经回路。

项目成果

Homosynaptic plasticity induction causes heterosynaptic changes at the unstimulated neighbors in an induction pattern and location-specific manner.

• DOI: 10.3389/fncel.2023.1253446
• 发表时间: 2023
• 期刊: FRONTIERS IN CELLULAR NEUROSCIENCE
• 影响因子: 5.3
• 作者: Argunsah, Ali Ozgur;Israely, Inbal
• 通讯作者: Israely, Inbal

The temporal pattern of synaptic activation determines the longevity of structural plasticity at dendritic spines.

• DOI: 10.1016/j.isci.2023.106835
• 发表时间: 2023-06-16
• 期刊: ISCIENCE
• 影响因子: 5.8
• 作者: Argunsah, Ali Ozgur;Israely, Inbal
• 通讯作者: Israely, Inbal

An interactive time series image analysis software for dendritic spines.

• DOI: 10.1038/s41598-022-16137-y
• 发表时间: 2022-07-20
• 期刊: SCIENTIFIC REPORTS
• 影响因子: 4.6
• 作者: Argunsah, Ali Ozgur;Erdil, Ertunc;Ghani, Muhammad Usman;Ramiro-Cortes, Yazmin;Hobbiss, Anna F.;Karayannis, Theofanis;Cetin, Mujdat;Israely, Inbal;Unay, Devrim
• 通讯作者: Unay, Devrim