Interactions of neural plasticity and behavior

大脑功能障碍会导致认知和情绪功能的变化，分析这些变化及其背后的机制可以让我们对大脑编码学习、记忆和情绪的方式有新的认识。这一提议的重点是当癫痫活动的发展是由对大鼠大脑区域的离散电刺激诱导时发生的行为变化，这种现象被称为点燃。我和我的同事们已经证明，特定的行为变化与特定部位的点燃有关。因此，行为变化必须与被刺激的大脑结构的变化相关联，而不是癫痫发作后发生的任何广泛的变化。我建议开始识别点燃后行为变化的机制。我将在几个不同和相互关联的分析水平上研究一些潜在的机制。分子：在点燃具有不同行为后果的大脑部位后，将评估基因和其合成受基因调控的蛋白质的变化，目的是确定特定部位的变化，这些变化可能与点燃该部位对行为的影响有关。细胞/形态：同样，我将研究点燃不同部位对海马神经细胞死亡或出生的影响，这是一个已知的显示细胞存在动态变化的区域。电生理学：我将确定点燃不同部位是否会对其他形式的神经可塑性产生不同的影响，包括海马神经元对大鼠在太空中位置的反应。系统和回路：我预测点燃靠近惊厥运动/行为底物的部位将显示出比较远部位更差的可塑性。我将检验这一预测。总体而言，这些研究应该确定癫痫导致学习和记忆中断的潜在机制，从而澄清正常参与这些认知活动的大脑区域的功能。

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.