The contribution of zincergic neurons to cerebral cortical plasticity

锌能神经元对大脑皮层可塑性的贡献

• 批准号: 217322-2009
• 负责人: Dyck, Richard
• 金额: $ 2.91万
• 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: 2013
• 资助国家: 加拿大
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=523759
• 关键词: contribution; zincergic; neurons; cerebral; cortical

All of the research in my laboratory, since its inception, has been directed toward gaining a better understanding of the intrinsic mechanisms that mediate and facilitate the remarkable malleability that is characteristic of the mammalian cerebral cortex. My perspective in the past was largely guided by studies of the postnatal development of cortex, as it is during this time that the neocortex is most plastic. It is our belief that the cellular and molecular mechanisms that underlie this plasticity are likely the same as are present in later development, and in old age, those that mediate processes such as learning and memory, and recovery from injury. The anatomical, molecular, physiological, and behavioural substrates that underlie the ability of neurons and neuronal networks in the cerebral cortex to alter their organization in response to changing sensory environments are largely unknown. However, it is known that neuronal activity profoundly affects the establishment and maintenance of neuronal circuits throughout the brain. In the most recent NSERC-funded granting period we have established abundant lines of evidence that implicate neurons that contain zinc in synaptic vesicles (are zincergic), and modulate the release of zinc in an activity- and experience-dependent manner, might play a special role in mediating synaptic plasticity within cerebral cortical circuits. Across this period of time we have also acquired a number of technologies that will allow us to better understand the specific role of zincergic neurons and synaptic zinc in mediating cerebral cortical plasticity. The tools include specific transgenic and knockout mice with altered expression of zinc signaling pathways, as well as the development of anatomical, molecular and physiological techniques and probes that allow us to monitor the activation zincergic signaling pathways. Using these novel tools, together with traditional physiological, anatomical, molecular and behavioural methodologies, we intend to continue our studies in rodent models to establish the role of zincergic neurons, and zinc itself, in the normal functioning and synaptic plasticity of cerebral cortical circuits.

我的实验室自成立以来，所有的研究都是为了更好地理解调节和促进哺乳动物大脑皮层显著可塑性的内在机制。我过去的观点很大程度上是由出生后大脑皮层发育的研究指导的，因为在这个时期，新大脑皮层是最具可塑性的。我们相信，这种可塑性背后的细胞和分子机制很可能与出现在后期发育和老年阶段的细胞和分子机制相同，这些机制介导了学习、记忆和损伤恢复等过程。大脑皮层中神经元和神经元网络响应感官环境变化而改变其组织的能力背后的解剖、分子、生理和行为基础在很大程度上是未知的。然而，众所周知，神经元活动深刻地影响着整个大脑神经元回路的建立和维持。在最近nserc资助的资助期内，我们已经建立了大量的证据，表明突触囊泡中含有锌（锌能）的暗示神经元，并以活动和经验依赖的方式调节锌的释放，可能在调节大脑皮层回路中的突触可塑性方面发挥特殊作用。在这段时间里，我们也获得了一些技术，这些技术将使我们更好地理解锌能神经元和突触锌在调节大脑皮层可塑性中的具体作用。这些工具包括特定的转基因和敲除小鼠锌信号通路的表达改变，以及解剖学，分子和生理技术和探针的发展，使我们能够监测锌能信号通路的激活。利用这些新工具，结合传统的生理学、解剖学、分子和行为学方法，我们打算在啮齿动物模型中继续我们的研究，以确定锌能神经元和锌本身在大脑皮层回路的正常功能和突触可塑性中的作用。