Identification of Core Pathways that Regulate Dendrite Morphology

Rutgers University New Brunswick, New Brunswick NJ

Investigators

Abstract

Firestein - Identification of Core Pathways that Regulate Dendrite Morphology Proposal 0548543 Abstract In order for proper neuronal function to occur, the neuron must have the correct number of input centers, or dendrites, which look like branches on a tree. However, very little is currently known about how the pattern of these branches is determined. The goal of Dr. Firestein's work is to identify core pathways by which dendrite number is regulated. Dr. Firestein will make use of molecular biology, biochemistry, and neuronal cell culture to investigate these pathways. First, Dr. Firestein will establish four criteria by which to characterize regulators of dendrite number. This system, not unlike criteria used to characterize neurotransmitters, will help to identify whether proteins reported in the literature are indeed members of core pathways for dendrite branching. Experiments will focus on two proteins, cypin and PSD-95, which Dr. Firestein believes to be components of the core pathway. Since the cytoskeleton, or supporting structure of a dendrite, must change when a dendrite branches, experiments will assess whether cypin and PSD-95 change dendrite number by altering the cytoskeleton. Second, the proposed studies will be extended to assess the role of other presumed proteins in the core program of dendrite branching. Other proteins will be tested to see if they they act together with cypin and PSD-95 by using cultured hippocampal neurons that have altered levels of these proteins. Finally, Dr. Firestein's group will take images of cultured hippocampal neurons over time using both static pictures and video microscopy and identify how dendrites form: via outgrowth, sprouting, or retraction. These studies are important because they will provide information on how dendrite branching is regulated during development to yield a functional brain. The impact of this research is far-reaching. The performance of the experiments will be part of a program to train undergraduate and graduate students in cutting-edge techniques in neuroscience and in practical aspects of experimental design and data interpretation. Furthermore, Dr. Firestein continues to mentor teachers on sabbatical from high school. By exposing high school teachers and students to experimental biology, the proposed research will motivate future scientists at a very early stage in their careers.