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: 2012
• 资助国家: 加拿大
• 起止时间: 2012-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=497265
• 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.

自从我的实验室开始以来，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非凡的可塑性的内在机制。我过去的观点很大程度上是由对皮质出生后发育的研究指导的，因为在这段时间里，新皮质最具可塑性。我们认为，这种可塑性背后的细胞和分子机制很可能与在后期发育中存在的相同，在老年时，那些调节学习和记忆以及从损伤中恢复的过程。大脑皮层神经元和神经元网络改变其组织以响应感觉环境变化的能力的解剖学、分子、生理和行为底物在很大程度上是未知的。然而，众所周知，神经元的活动深刻地影响着整个大脑神经回路的建立和维持。在最近由NSERC资助的授权期，我们已经建立了大量的证据表明，突触小泡中含有锌的神经元(锌能)，并以一种活动和经验依赖的方式调节锌的释放，可能在大脑皮层环路中调节突触可塑性方面发挥特殊作用。在这段时间里，我们还获得了许多技术，使我们能够更好地了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。这些工具包括锌信号通路表达改变的特定转基因和基因敲除小鼠，以及允许我们监控激活锌能信号通路的解剖学、分子和生理学技术和探针的开发。使用这些新的工具，结合传统的生理学、解剖学、分子和行为学方法，我们打算继续我们在啮齿动物模型中的研究，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。