In the developing visual system, the spatiotemporal patterns of visual inputs play an important role in shaping the connections of developing circuits. Using the developing retinotectal system of Xenopus tadpoles and a combination of in vivo whole cell recording and optical imaging techniques, we proposed to examine the development and experience-dependent refinement of visual circuits at the cellular level. In particular, we will examine the potential link between activity-dependent persistent synaptic modifications known as long-term potentiation/depression (LTP/LTD) and developmental refinement of visual circuits. The proposal consists of four parts. In PART I, we will examine the time course of synaptogenesis in the tectum, developmental changes in the synaptic function and plasticity and in the receptive field properties of tectal neurons, using a whole-cell recording method that allows the selective assessment of changes in glutamatergic and GABAergic/glycinergic inputs to the tectal neuron. The modulatory influence of GABAergic/glycinergic inputs on the development of receptive field properties will also be studied. In PART II, we will examine the effects of visual experience-evoked activity on retinotectal synapses and on the development of retinotopic map and receptive field properties. We will also determine the role of spike-timing dependent plasticity in the activity-induced refinement of retinotectal connections. In PART III, we will examine the relationship between activity-induced LTP/LTD and the structural refinement at identified retinotectal connections and the role of cooperative and competitive interactions among converging retinal inputs on the dendrite of single tectal neurons. Finally, in PART IV, we will examine the process by which visual input-induced LTP/LTD and structural modifications of retinotectal connections can be consolidated and become resistant to disruption by subsequent spontaneous spiking activity in the retinotectal system. Taken together, these in vivo studies provide unique opportunities to address several fundamental issues concerning the instructive function of sensory inputs in the refinement of developing neural connections, and are likely to yield new information relevant to our basic understanding of physiology and pathology of the developing nervous system.
