Molecular mechanisms of spatial memory

尽管过去二十年的研究结果激增，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背后的神经元和分子机制。我们最近发现，海马神经元中钙调神经磷酸酶的活性对于抑制空间学习过程中先前学到的不太有利的关联至关重要。钙调神经磷酸酶是一种钙依赖性酶，可促进许多对信号转导级联和神经元功能至关重要的蛋白质的去磷酸化。我们还发现海马神经元中的钙调神经磷酸酶活性会阻碍新的空间学习。这些观察结果表明，钙调磷酸酶作为分子开关发挥作用，决定海马介导的新学习与抑制先前学习的关联。抑制不需要的和不太有利的关联有助于提高认知和行为灵活性，对于所有生物体的生存和成功至关重要。我们提议进行一系列研究，以确定钙调神经磷酸酶参与空间学习和抑制先前学习的不利关联的神经元和分子机制。

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.