Our long-term objective is to understand the molecular and anatomical basis of cortical plasticity. Closely allied to this aim is to understand whether remote memory is based on cortical plasticity processes and more specifically whether remote memory depends on structurally based cortical plasticity. To these ends we will test two main hypotheses: that ? Animals showing remote but not short-term memory deficits will show experience-dependent cortical plasticity deficits ? Remote memory deficits will be associated with specific deficits in experience-dependent dendritic and spine plasticity By testing these hypotheses on mutants with deficits in both remote memory and cortical plasticity we will simultaneously begin to reveal the molecular basis of structural cortical plasticity. To test these hypotheses we plan to study four main properties of barrel cortex in animals generated by the remote memory screen: (1) the ability of barrel cortex to undergo experience-dependent plasticity (EDP), (2) normal anatomical and receptive field development of the cortex, (3) spine and bouton stability/turnover in whisker deprived and undeprived animals, (4) excitatory synaptic transmission and the ability to undergo spike-timing dependent plasticity (STOP). By identifying the mechanisms involved in remote memory and cortical plasticity, we may acheive several objectives: the capactiy for modification could be extended in cases of impaired development;insight could be gained into memory and learning deficits in adults;new approaches could be envisioned for restoring cortical function after brain damage. These objectives are therefore directly related to the agency's mission to improve public health because they are aimed at understanding processes that go wrong in disease conditions such as Alzheimer's and restoring function in trauma conditions such as stroke.
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