L-type calcium channels in memory

记忆中的L型钙通道

• 批准号: RGPIN-2018-04401
• 负责人: Yuan, Qi
• 金额: $ 3.06万
• 依托单位: Memorial University of Newfoundland
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=688497
• 关键词: type; calcium; channels; memory

Age-related cognitive decline and memory loss are associated with excess Ca2+ levels in brain cells. The L-type calcium channel (LTCC) is one of the major passages for Ca2+ entry into the cell and appears to mediate abnormal Ca2+ load in the aging brain cell. The paradox is that LTCCs are also an integral component of normal learning in animals and men. Our recent research has shown that without LTCCs, young animals cannot form long-lasting memory. The goal of our current research is to systematically characterize the role of LTCCs in learning in young and aged rats using odor associative learning as a model system, with the hypothesis that LTCCs will promote communication between neurons in the brain and memory formation in the young, but will suppress neuronal communications and lead to memory loss in aged subjects. ****** We will first test the expression levels of LTCCs in young adult and aged rats by measuring the amount of LTCC proteins in the cell membrane. We will then compare the functional roles of LTCCs in the two age groups using a go/no-go odor discrimination learning model. In this model, one odor is rewarded with water (positive odor), while another odor is not (negative odor). Thirsty rats learn to lick the water port when the positive odor is present but not when the negative one is present. We will measure how fast the rats learn and how long the memory for the odor and water association lasts. The effects of an LTCC blocker infusion to the brain on the speed of learning and the duration of the memory will be compared in the two age groups. We are also interested in how norepinephrine, a neuromodulator in the brain that promotes alertness and memory, interacts with LTCCs to influence their functions. Finally, we want to understand the mechanisms of how LTCCs differentially affect memories in the young and aged. We propose to study the cellular mechanisms of LTCC function in the brain slice, where neuronal communication can be recorded through electrodes. ****** Calcium is a central mediator for brain signaling, brain plasticity and learning. Systematic measurements of the roles of LTCCs in brain plasticity and learning in young and aged animals will provide fundamental insights on how calcium entry into the brain cell functions during development to influence memory formation. The results of this study could further direct brain research on memory loss prevention in the aging population.

与年龄相关的认知衰退和记忆丧失与脑细胞中过多的钙离子水平有关。L钙通道(LTCC)是钙离子进入细胞的主要通道之一，在衰老的脑细胞中可能介导异常的钙负荷。矛盾的是，LTCC也是动物和人类正常学习的一个组成部分。我们最近的研究表明，没有LTCC，幼年动物不能形成长期记忆。本研究的目的是以气味联想学习为模型系统，系统研究LTCCs在幼年和老年大鼠学习中的作用，假设LTCCs将促进年轻大鼠脑神经元之间的通讯和记忆的形成，但会抑制神经元通讯，导致老年大鼠记忆丧失。*我们将首先通过测量细胞膜上LTCC蛋白的数量来检测LTCC在年轻成年和老年大鼠中的表达水平。然后，我们将使用去/不去气味辨别学习模型来比较LTCC在两个年龄组中的功能作用。在这个模型中，一种气味会被水奖励(正面气味)，而另一种气味则不会(负面气味)。口渴的老鼠学会在有积极气味的时候舔水口，而不是在有负面气味的时候舔水。我们将测量老鼠学习的速度，以及对气味和水的记忆持续多久。在两个年龄组中，向大脑中注入LTCC阻滞剂对学习速度和记忆持续时间的影响将进行比较。我们还对去甲肾上腺素感兴趣，去甲肾上腺素是大脑中一种促进警觉性和记忆力的神经调节剂，它如何与LTCC相互作用来影响它们的功能。最后，我们想要了解LTCC如何不同地影响年轻人和老年人的记忆的机制。我们建议在脑片上研究LTCC功能的细胞机制，在脑片上，神经元的交流可以通过电极记录。*钙是大脑信号、大脑可塑性和学习的中心媒介。系统地测量LTCC在幼年和老年动物大脑可塑性和学习中的作用，将为钙离子在发育过程中进入脑细胞如何影响记忆形成提供基本的见解。本研究结果可进一步指导老龄人群预防记忆丧失的脑研究。