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.

摘要 大脑回路可以根据经验在结构上重新排列，突触连接可以增长和 被消灭了，即使是成年人。我们已经证明，在特定投入下的活动可以导致新的 蛋白质，或者促进单刺的持久生长，或者促进多个 增强后的突触。结构塑性过程中的这种相互作用之间的平衡可以是 在电路级的可塑性基础上，允许在树枝状区域内重新布线输入。然而， 为了能够实现这种重组，加强共同投入的机制以及 将需要那些将实现削弱和消除投入的措施。新蛋白质的合成 对信息的长期存储、长时间突触增强和结构可塑性至关重要。的 兴趣，这对长期形式的突触抑制也是必要的，而人们对此了解的要少得多 结构塑性的双向调节。除了这些Hebbian塑性过程之外，还有 动态平衡调节等可塑性形式影响树突状分支的可塑性。 稳态可塑性可以调节突触电流，也可以调节脊椎结构，并可以与Hebbian相互作用 在非活跃邻居处引发可塑性的可塑性。此外，神经元接受不同模式的活动在 它们的输入，目前还不清楚这些因素是如何影响结构可塑性的，或者它们是或多或少可能 受制于相互作用的输入之间的复杂集成。因此，使用双光子成像和谷氨酸 为了刺激和监测单个脊椎或定义的脊椎组的可塑性，我们将研究 不同形态的可塑性与脊柱结构变化的关系。具体来说，我们将确定 单次输入是否可以诱导突触抑制，这种形式的结构输出是什么 可塑性，以及在多个输入的蛋白质合成依赖的抑制是否可以经历竞争。 此外，我们将研究不同形式的活动之间相互作用的结构可塑性规则，如 当它们在多个输入的树状结构域内重合时，作为Hebbian和动态平衡可塑性。超越 这些形式的可塑性，我们也将研究非规则的活动模式，而不是泊松 分布，以建立对个人投入如何处理各种活动、它们如何 将这一点与共同活跃的邻居发生的事件结合起来，这些形式的可塑性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在分子、亚细胞和 电路水平突触相互作用的动力学，以及它们如何有助于建立和完善 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