Kindling, behavior, and hippocampal plasticity

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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.