Kindling, behavior, and hippocampal plasticity

点燃、行为和海马可塑性

• 批准号: 222912-2011
• 负责人: Kalynchuk, Lisa
• 金额: $ 2.91万
• 依托单位: University of Victoria
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=631401
• 关键词: Kindling; behavior; hippocampal; plasticity

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.

我们研究的总体目的是研究大脑的可塑性——大脑随着经历而改变的非凡能力。大脑的可塑性使我们每个人都独一无二。它为爱和依恋等积极情感、学习和记忆以及理解我们周围的世界提供了基础。然而，大脑的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导致脑细胞的异常兴奋或抑制，情绪和个性的改变，以及记忆的丧失。这种异常形式的大脑可塑性是我研究的重点。为了研究大脑的可塑性出错，我和我的学生们使用了一种叫做“点火”的啮齿动物模型。引燃是指每天对大脑特定区域进行短暂电刺激，导致运动性癫痫发作逐渐发展和加剧的过程。除了诱发癫痫的作用，点火还会使大脑中调节恐惧和认知的回路变得敏感。被点燃的老鼠表现出恐惧和记忆障碍，当老鼠接受更多的电刺激时，这些障碍的程度会增加。因此，点火为研究大脑可塑性的渐进变化如何随着时间的推移改变行为提供了难得的机会。本研究的目的是研究被称为海马体的大脑区域在点火产生的异常大脑可塑性中的作用。海马体对正常的认知和情感至关重要，它是成年后大脑中仅有的两个可以产生新细胞的区域之一。我们认为，点火改变了这种细胞诞生的过程，导致新细胞具有异常的特征和功能。这最终表现为老鼠的恐惧增加和记忆受损。我们建议通过一系列实验来验证这一观点，包括确定环境操纵（如暴露于富集和锻炼）是否可以恢复点燃大鼠正常的大脑可塑性。我们的实验结果将有助于确定成人大脑中细胞生成的功能后果，并有助于我们理解大脑的可塑性和行为。