Molecular mechanisms of spatial memory

空间记忆的分子机制

• 批准号: 238638-2013
• 负责人: Rajakumar, Nagalingam
• 金额: $ 1.82万
• 依托单位: University of Western Ontario
• 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=547049
• 关键词: Molecular; mechanisms; spatial; memory

Despite an explosion of findings in the past two decades, neurobiological mechanisms of learning and memory are still not clear. Our long-term goal is to determine neuronal and molecular mechanisms underlying spatial learning. We have recently identified that activity of calcineurin in hippocampal neurons is essential for the suppression of previously learned less-advantageous associations during spatial learning. Calcineurin is a calcium-dependent enzyme that facilitates dephosphorylation of a number of proteins critical in signal transduction cascades and neuronal function. We have also found that calcineurin activity in hippocampal neurons blocks new spatial learning. These observations indicate that calcineurin functions as a molecular switch that determines hippocampus-mediated new learning versus suppressing previously learned associations. Suppressing unwanted and less-advantageous associations contributes to cognitive and behavioral flexibility and is essential for the survival and success in all organisms. We are proposing to undertake a series of studies to determine neuronal and molecular mechanisms underlying the involvement of calcineurin in spatial learning and suppression of previously learned disadvantageous associations.

尽管在过去的二十年里发现了爆炸性的发现，但学习和记忆的神经生物学机制仍然不清楚。我们的长期目标是确定空间学习的神经元和分子机制。我们最近发现，海马神经元中钙调磷酸酶的活性是必不可少的抑制以前学到的不太有利的协会在空间学习。钙调神经磷酸酶是一种钙依赖性酶，其促进在信号转导级联和神经元功能中至关重要的许多蛋白质的去磷酸化。我们还发现海马神经元中的钙调磷酸酶活性阻断了新的空间学习。这些观察结果表明，钙调神经磷酸酶作为一个分子开关，决定海马介导的新的学习与抑制以前学习的协会。抑制不想要的和不太有利的协会有助于认知和行为的灵活性，是所有生物体生存和成功的关键。我们建议进行一系列的研究，以确定神经元和分子机制的钙调磷酸酶参与空间学习和抑制以前学习的不利协会。