Molecular regulation of synaptic growth
Office Phone: 265-4813
Lab Website: O'connor-Giles Laboratory
Research Strengths: Development, Plasticity and Repair
Neurons function within neural circuits to regulate behaviors ranging from simple reflexes to learning and memory. Synapses - the connections between neurons and their targets - are the functional units of neural circuits. We are interested in how neurons build synaptic connections and modulate their strength. Synapses comprise a presynaptic active zone that is responsible for the Ca2+ dependent release of neurotransmitter-filled synaptic vesicles in response to action potentials. This signal is received by neurotransmitter receptors that cluster opposite active zones at postsynaptic densities. Synapse formation is a complex process that depends on intercellular communication between pre and postsynaptic cells – often at sites very distant from cell bodies. In fact, a single central neuron can form thousands of synapses and must independently regulate the development of each. Synapses must also maintain the life-long ability to modify their morphology and physiology in response to environmental stimuli and changes in activity levels – modifications that are thought to underlie learning and memory.
Defects in synaptic development and plasticity are associated with a broad range of neurological disorders including developmental disorders such as autism; motor, cognitive and psychological impairments; and neurodegeneration. Thus, the identification and characterization of the molecules that regulate synapse formation and function is key to our understanding of normal neural function and our ability to treat a variety of neurological disorders. The Drosophila larval NMJ is an ideal model system for elucidating the general principles underlying synaptogenesis. In addition to highly amenable genetics, the Drosophila NMJ is readily accessible for imaging and electrophysiological analysis. Importantly, the molecules and mechanisms implicated in synaptogenesis at the Drosophila NMJ are remarkably conserved.
Bruckner, J*., Gratz, S*., Slind, J., Geske, R., Cummings, A., Galindo, S., Donohue, L. and O’Connor-Giles, K. (2012). Fife, a Drosophila Piccolo-RIM homolog, promotes active zone organization and neurotransmitter release.J Neurosci. 32(48), 17048-58.
Babaoglan, A.B., K.M. O’Connor-Giles, H. Mistry, A. Schickedanz, B.A. Wilson, and J.B.2009. Skeath. Sanpodo: a context-dependent activator and inhibitor of Notch signaling during asymmetric divisions. 2009 December 15; 136(24): 4089–4098. doi:10.1242/dev.040386
O’Connor-Giles, K.M. and B. Ganetzky. 2008. Satellite Signaling at Synapses. Fly 2:259-61.
O’Connor-Giles, K.M., L.L. Ho, and B. Ganetzky. 2008. Nervous wreck interacts with Thickveins and the endocytic machinery to attenuate retrograde BMP growth signaling during synaptic growth. Neuron 58:507-518.
O’Connor-Giles, K.M. and J.B. Skeath. 2003. Numb inhibits membrane localization of Sanpodo, a four-pass transmembrane protein, to promote asymmetric divisions in Drosophila. Dev. Cell 5:231-43.