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: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=746273
• 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.

与年龄相关的认知能力下降和记忆力丧失与脑细胞中过量的 Ca2+ 水平有关。 L 型钙通道 (LTCC) 是 Ca2+ 进入细胞的主要通道之一，似乎介导衰老脑细胞中异常的 Ca2+ 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，如果没有 LTCC，幼年动物就无法形成持久记忆。我们当前研究的目标是使用气味联想学习作为模型系统，系统地表征 LTCC 在年轻和老年大鼠学习中的作用，假设 LTCC 会促进大脑神经元之间的通讯和年轻大鼠的记忆形成，但会抑制老年受试者的神经元通讯并导致记忆丧失。 我们将首先通过测量细胞膜中 LTCC 蛋白的量来测试年轻成年和老年大鼠中 LTCC 的表达水平。然后，我们将使用通过/不通过气味辨别学习模型来比较 LTCC 在两个年龄组中的功能作用。在此模型中，一种气味会受到水的奖励（正气味），而另一种气味则不会（负气味）。当出现阳性气味时，口渴的老鼠会学会舔水口，但当出现阴性气味时，则不会。我们将测量老鼠的学习速度以及气味和水关联的记忆持续多长时间。将比较两个年龄组的大脑输注 LTCC 阻滞剂对学习速度和记忆持续时间的影响。我们还对去甲肾上腺素（一种大脑中促进警觉性和记忆力的神经调节剂）如何与 LTCC 相互作用以影响其功能感兴趣。最后，我们想要了解 LTCC 如何差异影响年轻人和老年人的记忆的机制。我们建议研究大脑切片中 LTCC 功能的细胞机制，其中神经元通讯可以通过电极记录。 钙是大脑信号传导、大脑可塑性和学习的中心介质。对 LTCC 在年轻和老年动物大脑可塑性和学习中的作用进行系统测量，将为了解发育过程中钙进入脑细胞如何发挥作用以影响记忆形成提供基本见解。这项研究的结果可以进一步指导预防老年人记忆丧失的大脑研究。