Interactions of neural plasticity and behavior

大脑功能障碍会导致认知和情感功能的变化，对这些变化及其机制的分析可以对大脑编码学习、记忆和情感的方式产生新的见解。 该建议的重点是当癫痫活动的发展由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，行为变化必须与大脑结构的刺激变化有关，而不是与癫痫发作后发生的任何广泛变化有关。 我建议开始确定点燃后行为变化的机制。 我将在几个不同的和相互关联的分析层次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特定变化，这些变化可能与点燃该部位的行为影响有关。 细胞/形态学：同样，我将研究点燃不同部位对海马体神经细胞死亡或出生的影响，海马体是一个已知的显示细胞存在动态变化的区域。 电生理学：我将确定是否点燃不同的网站差异影响其他形式的神经可塑性，包括海马神经元的反应大鼠的空间位置。 系统和电路：我预测，点燃的网站接近运动/行为基板的抽搐将显示较低的可塑性比更遥远的网站，我将测试的预测。 总的来说，这些研究应该确定潜在的癫痫诱导的学习和记忆中断的机制，从而澄清通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.