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 this project is to identify how both global and local changes in dendrite branching occurs. The Principal Investigator and her students will make use of molecular biology, biochemistry, and neuronal cell culture to study signaling by brain-derived neurotrophic factor (BDNF), a major regulator of dendrite branching. First, they will assess how administration of BDNF to neurons changes the shape of the dendrites overall and at distinct regions from the cell body. Second, neurons will be exposed to BDNF-coated latex beads to mimic local stimulation, and changes in the dendrite branching by this treatment will be compared to those that occur with global BDNF treatment. Third, they will use drugs and molecular techniques to identify the proteins that are responsible for the effects of BDNF. 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. Conducting the experiments will not only advance our understanding of how dendrite morphology is regulated but will also be part of a program to train high school, undergraduate, and graduate students in cutting-edge techniques in neuroscience. The project involves setting up an exchange program for undergraduate and Masters students at the University of Liberia so that they can perform summer research in the Firestein laboratory. A major goal is to establish an international program to bring neuroscience to the University of Liberia community through seminars, workshops, and exchange programs. This program will help educate people in a country facing global conflict.
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 or how these branches change when a person learns. Brain-derived neurotrophic factor (BDNF) is a potent stimulator of dendrite growth. BDNF can be released onto specific sites on dendrites of neurons, called synapses, that serve as communication centers between neurons. It can also be released by support cells in the brain, called astrocytes, in large quantities, resulting in exposure of the entire neuron to BDNF. These two different types of release of BDNF may affect dendrites differently, resulting in differences in neuron signaling and learning and memory. This project analyzed the differences in changes to dendrites on neurons from the region of the brain involved in learning and memory, called the hippocampus, by these different modes of BDNF exposure: local versus global. Results from the experiments show that localized BDNF treatment alters overall dendrite branching in a different manner than does global treatment. Global treatment results in activation of a key signaling pathway that we have studied extensively and includes dendrite branching mediated by the protein cypin. Global BDNF exposure increases dendrites close to the cell body whereas local exposure increases dendrites close to the sites of exposure, whether close to or far away from the cell body. Thus, the different modes of BDNF exposure on neurons distinctly regulate the shape of dendrites, potentially resulting in different signaling between neurons and contributing to different aspects of neuron function, such as learning. In addition, conducting these experiments has advanced our understanding of how dendrite morphology is regulated and included the training of K-12 biology teachers, and high school, undergraduate, and graduate students, including underrepresented individuals and women, in cutting-edge neuroscience and experimental design and data interpretation. Broader impacts of this research include the following. Dr. Firestein acts as faculty advisor to the Cell Biology/Neuroscience Society and President of the NJ Chapter of the Society for Neuroscience (NJ-SfN) to encourage the Rutgers and the general NJ communities to learn about neuroscience. As part of this plan, Dr. Firestein organized "Cutting Edge Neuroscience: From the Bench to Publishing," a gathering of NJ Chapter SfN members, neuroscientists, and members of the public from NJ, NY, and PA. This was the first symposium of its kind in the area. Dr. Firestein also held Neuroscience Days at Rutgers University, where students from surrounding middle schools were given age appropriate lectures on the brain and performed sheep brain dissection and made models of neurons.
