ROLE OF ACTIVITY IN SYNAPSE COMPETITION STUDIED IN GENETIC ENGINEERED MICE

The proposed projects aim at inducing a selective and drastic reduction of the activity of specific muscular and neuronal cells in order to, a) create animal models of human neurological disease, b) provide insights into the global function of specific sets of neurons in the adult and c) provide information on the mechanisms at work during perinatal development and the repair of lesion in the adult. We utilize a series of genetic approaches to induce electrical silence in neurons and muscle fibers. This is based on the expression of a chloride channel in these cellular elements thus rendering them inactive, in order to investigate the role of action potential activity in normal development of synapses in the neuromuscular system and in a related neuro-neuronal model, the olivary neuron-Purkinje neuron pathway. In particular we focus our efforts in improving our understanding of the mechanisms underlying synapse competition and elimination, a striking and widespread process in the development of peripheral and central nervous system. Finally we hope that the various genetic techniques used by us in experimental rodents, may help create models for therapeutic approaches in human neuromuscular diseases.