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: 9974133
• 负责人: Inbal Israely
• 金额: $ 38.86万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9974133
• 关键词: Adult; Affect; Body Weight Changes; Brain; Calcium; Chemosensitization; Complex; Dendritic Spines; Dependence; Development; Electrophysiology (science); Equilibrium; Event; Functional disorder; Glutamates; Goals; Growth; Hippocampus (Brain); Image; Individual; Information Storage; Lead; 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; base; 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 脑电路可以通过经验进行结构重新排列，突触连接可以增长并成为 即使在成年人中也被淘汰。我们已经表明，特定输入的活动可以导致新的生产 蛋白质，促进单个刺的持久生长，或多个蛋白质的合作与竞争 增强后突触。结构可塑性期间这种相互作用之间的平衡可能是 在电路水平上可塑性的基础，这允许在树突状域内重新布线输入。然而， 为了能够实现这种重组，加强共同投入的机制以及 那些将需要减弱和消除投入的人。新蛋白的合成 对于长期存储信息，持久的突触增强和结构可塑性至关重要。的 兴趣，这对于长期持久的突触抑郁症也是必要的，而对 结构可塑性的双向调节。除了这些Hebbian可塑性过程外， 可塑性的形式，例如体内稳态调节，影响树突分支的可塑性能力。 稳态可塑性可以扩展突触电流以及脊柱结构，并可以与Hebbian相互作用 可塑性以引起非活跃邻居的可塑性。此外，神经元在 它们的输入，尚不清楚这些效果如何结构可塑性，或者它们是否或多或少是可能的 如果共同活性输入之间的复杂整合。因此，使用两光子成像和谷氨酸 启动和监测单个刺或定义的棘突的可塑性，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 是否可以在单个输入处诱导突触抑郁症，这种形式的结构输出是什么 可塑性以及蛋白质合成是否依赖于多个输入的抑郁症会发生竞争。 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， 作为Hebbian和稳态可塑性，当它们在多个输入的树突状域中重合时。超过 这些形式的可塑性，我们还将研究非规范的活性模式，而托有泊松 分发，以建立对个人投入如何处理各种活动的理解，他们如何 将其与共同活性邻居的事件结合在一起，以及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在分子，亚细胞和 电路水平突触相互作用的动态，以及它们如何贡献和改进 认知功能所需的神经回路。