Scholar Profile

Kendal S. Broadie

Professor
Department of Biological Sciences
Vanderbilt University
VU Station B
Nashville, TN 37235-1634
Voice: 615-936-3937(office); 615-936-3935, -3936 (lab)
Fax: 615-936-0129
Email: kendal.s.broadie@vanderbilt.edu
Personal Homepage
1997 Searle Scholar

Research Interests

Synaptogenesis, Synaptic Function, Learning and Memory, Behavior/Epilepsy

The development and function of the brain is one of the most fascinating and perplexing puzzles known to us. How can we even begin to understand higher brain function: coordinating movement, behavior, learning and memory? The reductionist philosophy of our research effort is to dissect the puzzle into its simplest elements and attempt to understand the whole from the analysis of fundamental principles. First, we focus on the synapse as the key communication link between the working elements of the brain, the neurons. Second, we use a simple model synapse, the neuromuscular junction (NMJ) which, unlike central synapses, is amenable to highly detailed developmental and functional analyses. Third, we use a model genetic organism, the fruitfly Drosophila melanogaster, which allows us to systematically identify and remove each genetic component of the synapse in order to assay its function. We are using this simple, genetic model system to ask three questions: 1) How does a synapse develop?, 2) How does a synapse function?, and 3) How does a synapse maintain adaptive plasticity?

There are two aspects of synaptic development: specificity and construction of the communication link. Specificity is determined when the appropriate synaptic partners find and recognize each other in the developing embryo. The Drosophila system is particularly well suited to tackle this question since the cells are individually identifiable and Drosophila is among the best understood systems at a molecular genetic level. Following target recognition, the communication link is constructed by aligning the presynaptic signaling field with the postsynaptic receptor field. The Drosophila NMJ is an excellent system to address this developmental program since the synapse can be monitored both physiologically and morphologically as it develops in vitro or in vivo. Thus, the entire process of synaptogenesis can be assayed and systematically dissected through the isolation and study of genetic mutants.

The function of the synapse is to translate electrical information into chemical information and back again. Presynaptically, this information transfer requires mechanisms to couple an action potential to the fusion of neurotransmitter vesicles. The molecular machinery of the synaptic vesicle cycle has been conserved from humans to Drosophila and we are currently engaged in the systematic isolation and mutation of these genes. Postsynaptically, information transfer requires a receptor field and downstream signaling pathways. The Drosophila NMJ is a glutamatergic synapse, similar to those found in the human CNS, and the glutamate receptor has been molecularly characterized. We are just beginning to unravel the downstream postsynaptic signaling cascades. A combination of forward and reverse genetic techniques should lead to a complete understanding of the functional properties of the synapse.

The function of the synapse is to translate electrical information into chemical information and back again. Presynaptically, this information transfer requires mechanisms to couple an action potential to the fusion of neurotransmitter vesicles. The molecular machinery of the synaptic vesicle cycle has been conserved from humans to Drosophila and we are currently engaged in the systematic isolation and mutation of these genes. Postsynaptically, information transfer requires a receptor field and downstream signaling pathways. The Drosophila NMJ is a glutamatergic synapse, similar to those found in the human CNS, and the glutamate receptor has been molecularly characterized. We are just beginning to unravel the downstream postsynaptic signaling cascades. A combination of forward and reverse genetic techniques should lead to a complete understanding of the functional properties of the synapse.

The function of the synapse is to translate electrical information into chemical information and back again. Presynaptically, this information transfer requires mechanisms to couple an action potential to the fusion of neurotransmitter vesicles. The molecular machinery of the synaptic vesicle cycle has been conserved from humans to Drosophila and we are currently engaged in the systematic isolation and mutation of these genes. Postsynaptically, information transfer requires a receptor field and downstream signaling pathways. The Drosophila NMJ is a glutamatergic synapse, similar to those found in the human CNS, and the glutamate receptor has been molecularly characterized. We are just beginning to unravel the downstream postsynaptic signaling cascades. A combination of forward and reverse genetic techniques should lead to a complete understanding of the functional properties of the synapse.