Kindling, behavior, and hippocampal plasticity

我们研究的总体目的是研究大脑的可塑性--大脑随着经验而变化的非凡能力。大脑的可塑性使我们每个人都独一无二。它为爱和依恋的积极情绪提供了基础，为学习和记忆以及理解我们周围的世界提供了基础。然而，大脑可塑性是一把双刃剑：在某些情况下，大脑活动的不断重塑也会促进脑细胞的异常兴奋或抑制，改变情绪和个性，失去记忆。这种大脑可塑性的异常形式是我研究的重点。为了研究大脑的可塑性出了问题，我和我的学生利用了一种名为点燃的啮齿动物模型。点燃是一个过程，通过每天对特定大脑区域进行短暂的电刺激，导致运动性癫痫的逐渐发展和加剧。除了引发癫痫的作用外，点燃还会使大脑中调节恐惧和认知的回路变得敏感。点燃的大鼠表现出恐惧和记忆障碍，随着大鼠接受更多的电刺激，这些损伤的幅度会增加。因此，点燃提供了一个难得的机会来研究大脑可塑性的渐进性变化如何随着时间的推移改变行为。这项拟议的研究的目的是调查被称为海马体的大脑区域在点燃产生的异常大脑可塑性中所起的作用。海马体对正常的认知和情绪至关重要，它是大脑中仅有的两个成年后可以产生新细胞的区域之一。我们认为，点燃改变了这个细胞的诞生过程，导致新的细胞具有异常的特征和功能。这最终表现为点燃的大鼠恐惧增加和记忆力受损。我们建议在一系列实验中测试这一想法，包括确定环境操作，如暴露在丰富和锻炼中是否可以恢复点燃大鼠的正常大脑可塑性。我们的实验结果将有助于确定成人大脑中细胞出生的功能后果，并有助于我们理解大脑的可塑性和行为。

The general purpose of our research is to study brain plasticity--the remarkable ability of the brain to change with experience. Brain plasticity is what makes each one of us unique. It provides a substrate for the positive emotions of love and attachment, for learning and remembering, and for understanding the world around us. However, brain plasticity is a double-edged sword: Under certain circumstances, the constant re-shaping of brain activity can also promote abnormal excitation or inhibition of brain cells, altered emotion and personality, and lost memories. This aberrant form of brain plasticity is the focus of my research. To study brain plasticity gone awry, my students and I make use of a rodent model called kindling. Kindling is a process by which daily brief electrical stimulation of specific brain regions results in the gradual development and intensification of motor seizures. In addition to its epileptogenic effects, kindling also sensitizes circuits in the brain that regulate fear and cognition. Kindled rats show fear and memory impairments that increase in magnitude as the rats receive a greater number of electrical stimulations. Kindling thus provides a rare opportunity to study how progressive changes in brain plasticity can alter behavior over time. The objective of the proposed research is to investigate the role of a brain region called the hippocampus in the aberrant brain plasticity produced by kindling. The hippocampus is critical for normal cognition and emotion, and it is one of only two regions of the brain where new cells can be born in adulthood. We believe that kindling alters the process of this cell birth, leading to new cells with abnormal characteristics and functioning. This ultimately manifests itself as increased fear and impaired memory in kindled rats. We propose to test this idea in a series of experiments, including determining whether environmental manipulations such as exposure to enrichment and exercise can restore normal brain plasticity in kindled rats. The results of our experiments will help identify the functional consequences of cell birth in the adult brain and aid in our understanding of brain plasticity and behavior.