The research proposed here will investigate the electrophysiological events and molecular components underlying activity-dependent synapse maturation. Experiments will examine factors influencing the developmental transition from """"""""silent"""""""", purely NMDA receptor mediated, to """"""""functional"""""""" synapses containing both NMDA and AMPA receptors. Whole-cell and perforated patch recording from intact Xenopus tadpole tectum will be combined with recombinant viral transformation for expression of both normal and mutated plasticity-related genes, such as CaMKII. Attention will be focused on the similarity between activity- dependent synapses maturation and """"""""classical"""""""" models of synaptic plasticity, such as long-term potentiation (LTP) and depression (LTD) in the hippocampus and neocortex.
The specific aims of this proposal are: number 1. To test the hypothesis that different patterns of excitatory retinotectal synaptic activity can lead to long-term potentiation or depression of developing retinotectal synapses. Number 2. To determine the mechanisms for induction of activity-dependent synaptic plasticity in the tectum. Number 3. To elucidate the role of CaMKII and calcineurin in activity-dependent plasticity. Number 4. To determine if GABAergic transmission in the developing tectum is excitatory, and whether GABAergic depolarization can contribute to maturational plasticity. The results from these studies will greatly advance the understanding of how neuronal activity promotes synapse formation and stabilization, or, destabilization and retraction.
