9808723 POO During the early development of the nervous system, the sensory inputs from the environment received by the central nervous system play a critical role. Abnormal sensory inputs result in abnormal development of nerve connections in the brain. However, how sensory inputs affect these connections is poorly understood. In this project, Dr. Poo and a graduate student and postdoctoral fellow will use an electrical recording method that can detect the efficiency of nerve connections in the intact visual system of the developing frog tadpole. In particular, they will examine how nerve connections from the retina to its major target in the brain, the tectum, are affected by electrical activity in the visual inputs. In Part I of the project, they will determine how repetitive activity induced by electrical stimulation of retinal neurons affects the efficiency of the synaptic connections between the retina and tectum, or retino-tectal synapses. The patterns of electrical activity and the cellular mechanisms that produce long-term changes in efficiency, namely long-term potentiation and/or depression (LTP & LTD) will be examined. In Part II, they will use light stimuli to initiate localized retinal activity and examine whether physiological visual stimuli can induce LTP or LTD of retino- tectal synapses, and if so, how these light-induced synaptic modifications relate to those produced by direct electrical stimulation. In Part III, they will carry out simultaneous electrophysiological and optical recording of identified retino- tectal projections in the tectum, using a newly developed high- resolution microscopic technique called two-photon laser scanning fluorescence microscopy. They will determine whether and how electrical and visual stimuli shape the pattern of axonal processes of retinal ganglion neurons and dendritic processes of the postsynaptic tectal cells. This project offers unique opportunities for direct examination of the effects of se nsory activity on the structure and function of synaptic connections in an intact visual system. The information obtained will be valuable to our understanding of the development of vertebrate visual systems and plasticity of neuronal connections in general.