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2015 Grants - DeFelipe
The Pyramidal Neuron in Cognition and Alzheimer’s Disease
Javier DeFelipe, Ph.D.
Spanish National Research Council
2015 Zenith Fellows Award
The brain has many different regions with specific functions, each containing nerve cells (neurons) that are interconnected in distinct ways. A feature that sets humans apart from other animals is the size and degree of complexity of the top, outermost layer of the brain, known as the cerebral cortex. The cerebral cortex is responsible for many of our most advanced capabilities, such as speaking, writing and advanced thinking.
Although the cerebral cortex contains many types of nerve cells, the most prominent are known as pyramidal cells, because they are shaped like pyramids with long, branching extensions that form many connections with other nerve cells. Pyramidal cells are damaged in the early stages of Alzheimer’s disease, but scientists do not yet have a complete understanding of how this damage may contribute to the losses in brain function that accompany Alzheimer’s disease.
Dr. Javier DeFelipe, Ph.D., and colleagues have proposed a series of experiments to understand how Alzheimer’s disease alters the structure of pyramidal cells. They will examine how these changes impact the ability of pyramidal cells to connect and communicate with other nerve cells, and how this may relate to the loss of brain function observed in people with Alzheimer’s disease. Dr. DeFelipe and colleagues will study brain tissue from people who had Alzheimer’s disease and examine how alterations in pyramidal cells relate to cognitive decline.
The researchers will inject a dye into individual pyramidal cells in the cerebral cortex and then use a new technique known as focused ion beam/scanning electron microscopy (FIB/SEM) to visualize the three-dimensional structure of each pyramidal cell and examine the places where they connect to other nerve cells. By comparing healthy brains to brains affected by Alzheimer’s disease, the researchers will study how the disease process affects the structure and connections of pyramidal cells. These studies will help scientists better understand the relationship between damage to nerve cells and impairments in brain function in Alzheimer’s disease.