Interactions of neural plasticity and behavior

点击翻译按钮获取中文摘要

Brain dysfunction can lead to changes in cognitive and emotional functions, and analysis of the changes and the mechanisms underlying them can lead to new insight into the ways the brain encodes learning, memory, and emotion.  The focus of this proposal is the changes in behavior that occur when the development of epileptic activity is induced by discrete electrical stimulation of regions of the rat brain, a phenomenon referred to as kindling.  My colleagues and I have demonstrated that specific  behavioral changes are associated with kindling of particular sites.  Hence behavioral change must be associated with changes in the brain structure stimulated, and not with any widespread changes that occur following seizures.  I propose to begin to identify the mechanisms of behavioral change following kindling.  I will investigate a number of potential mechanisms, at several different and inter-related levels of analysis.  Molecular:  Changes in genes and in the proteins whose synthesis is regulated by genes will be assessed after kindling of brain sites that have different behavioral consequences, with the goal of identifying changes specific to a particular site that might be related to the effects on behavior of kindling that site.  Cellular/morphological:  Similarly, I will examine the effects of kindling different sites on death or birth of nerve cells in the hippocampus, a region known to show dynamic changes in cellular existence.  Electrophysiological:  I will determine whether kindling of various sites differentially affects other forms of neural plasticity, including the responsiveness of hippocampal neurons to the rat's position in space.  Systems and circuits:  I predict that kindling of sites close to the motor/behavioral substrates of convulsions will show less plasticity than more distant sites, and I will test the prediction.  Collectively these studies should identify potential mechanisms underlying epilepsy-induced disruption of learning and memory and thereby clarify the functions of brain regions normally participating in these cognitive activities.