| |
|
|
The
completion of the genome sequence of Drosophila melanogaster has provided
a unique opportunity to initiate a new phase of systematic gene analysis of
neuronal function. Although Drosophila as an experimental organism has
made fundamental contributions to the fields of heredity and developmental
biology, the field of neurobiology has also taken advantage of the powerful
genetic techniques afforded by the fruitfly. Seymour Benzer and colleges
identified and analyzed mutants with a variety of behavioral defects caused by
single gene mutations. Such behavioral mutants initiated a wave of genetic
studies into the function of the nervous system and led to the characterization
of mutants such as Shibire and Shaker. These studies provided the
foundation for a new generation of fly neurobiologists that employed systematic
genetic screens for specific neurological phenotypes. The ease of performing
electrophysiological analysis at Drosophila neuromuscular junctions
readily complements the genetic approaches available in flies, making it an
important model system for understanding synaptic function and development, as
well as membrane excitability and neurological disease.
Using the fruit fly Drosophila as a model, the
Littleton laboratory seeks to elucidate the molecular mechanisms underlying
synapse formation, function and plasticity by combining molecular biology,
protein biochemistry, electrophysiology and imaging approaches with genetics. In
addition, studies are underway to characterize how the connections among neurons
change during learning and memory. The lab has identified many previously
unsuspected gene candidates in the fly brain for activity-dependent modulation
of neuronal function and is determining how these genes contribute to cellular
forms of behavioral plasticity. In addition, the lab is interested in the
alterations in neuron-to-neuron signaling and connections that underlie
epilepsy, Huntington’s disease, Autism and other genetically complex neurological
disorders. Together, these approaches should greatly expand the understanding of
the basic mechanisms of synapse function and plasticity, as well as provide
insights into expression changes that allow synaptic ensembles to store
information through changes in neuronal connectivity and function.
|