Molecular mechanisms of spatial memory

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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.