One of the most significant advances in our understanding of development of the brain during the past two decades is the realization that nerve connections made during embryonic life undergo substantial rearrangement as the nervous system matures. Some connections are eliminated, while others become strengthened and stabilized. Evidence suggests that this rearrangement results from a competitive interaction between adjacent nerve connections in a manner that depends upon the pattern of nerve activity, which is in turn triggered by the sensory input from the environment. This activity-dependent competition between adjacent connections has been observed in both central and peripheral nervous systems, but the mechanism responsible for this phenomenon is poorly understood. In the previous granting period of this project, it was discovered that activity-dependent competition can be observed in isolated synaptic connections in a simple cell culture. This finding opens the possibility of experimentally addressing the problem of synaptic competition effectively at cellular and molecular levels. In the present project, a series of experiments will be carried out that will result in an insight into the mechanism responsible for modulating the strength of synaptic connections. This should lead to an understanding of how adjacent synapses on a single postsynaptic cell compete for survival and of the physiological and morphological changes at the synapse during the process of synaptic competition. The results from these studies will help us to understand how nerve connections are modified during development of the nervous system.
