Mechanisms underlying short-term synaptic plasticity between identified neurons

已识别神经元之间短期突触可塑性的潜在机制

• 批准号: 155078-2010
• 负责人: Syed, Naweed
• 金额: $ 2.4万
• 依托单位: University of Calgary
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2014
• 资助国家: 加拿大
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=545625
• 关键词: Mechanisms; underlying; short; term; synaptic

All nervous system functions rely upon neuronal communications through specialized structure, termed synapse. Diffusion of electrical activity-induced, neurotransmitters across the synaptic cleft and its activation of juxtaposed receptors on the recipient cell enable the flow of information across all brain circuits. Failure of this neuronal communication renders the brain dysfunctional. Despite extensive research in the field of neuroscience, the precise cellular and molecular mechanisms that regulate various modes of synaptic communications remain, however, largely unknown. Moreover, even less is known about the mechanisms that enable neurons to either increase or decrease their synaptic strength (synaptic plasticity) in response to a changing environment. We have developed a simple model comprising of functionally defined neurons from the snail. This model has not only allowed us to define mechanisms underlying synaptic transmission, but has also helped design silicon chips that can be interfaced with brain cells. Using this model, we will now define both cellular and molecular pathways that regulate not only the synaptic transmission, but also the short-term synaptic plasticity that forms the basis for learning and memory. Neuronal networks will be reconstructed in cell culture and using several state-of-the-art neuroscience techniques, we will identify mechanisms that regulate neuronal communication under normal conditions and after short-term synaptic plasticity that form the basis for learning and memory. We will seek to determine how calcium entry into neurons activates a cascade of second messengers that in turn affect neuronal output during working memory.

所有神经系统的功能都依赖于通过称为突触的专门结构进行的神经元通信。 电活动诱导的神经递质穿过突触间隙的扩散及其对受体细胞上并列受体的激活使信息能够在所有脑回路中流动。 这种神经元通信的失败会使大脑功能失调。 尽管在神经科学领域进行了广泛的研究，但调节突触通信的各种模式的精确细胞和分子机制在很大程度上仍然未知。 此外，我们对神经元能够根据环境变化增加或减少突触强度（突触可塑性）的机制知之甚少。 我们已经开发了一个简单的模型，包括功能定义的神经元从蜗牛。 这一模型不仅使我们能够定义突触传递的机制，而且还帮助设计了可以与脑细胞连接的硅芯片。 使用这个模型，我们现在将定义细胞和分子通路，这些通路不仅调节突触传递，而且调节形成学习和记忆基础的短期突触可塑性。 神经元网络将在细胞培养中重建，并使用几种最先进的神经科学技术，我们将确定在正常条件下和形成学习和记忆基础的短期突触可塑性后调节神经元通信的机制。 我们将试图确定钙进入神经元如何激活第二信使的级联反应，进而影响工作记忆过程中的神经元输出。