Activity-dependent synaptic plasticity plays an important role in the refinement of nerve connections during development of the nervous system. This proposal aims to shed more light on this process by determining the causal relationship between activity-induced changes in synaptic strength, namely long-term potentiation (LTP) and long-term depression (LTD), and structural modification of the connections. Though much has been learned about functional plasticity of synapses (such as LTP and LTD) and structural remodeling of connections during development, the relationship between them has not been clearly determined. I propose to examine the causal relationship between changes in synaptic strength and structural remodeling in the developing Xenopus retinotectal system. In this in vivo system, persistent changes in synaptic strength (LTP/LTD) can be induced by either electrical or visual stimulation and changes in morphology can be readily examined by two-photon microscopy. Structural changes have been observed after induction of LTP in the hippocampus, which is reflected as increased spine density and motility, growth of filopodia and formation of new spines and synapses with perforated post-synaptic densities. In addition, expression of LTP can be partially blocked by drugs interfering with the function of cytoskeleton. However, there are a few questions remaining to be answered: Do changes in structure observed with LTP also occur in vivo during normal development? Are changes in structure necessary for the long-term maintenance of LTP? Can induction of LTD cause structural changes, perhaps in the opposite direction of those caused by LTP? I will address these questions using simultaneous in vivo patch recording and two-photon imaging in Xenopus retinotectal system.
