NEURAL ACTIVITY, NEURON-GLIA RELATIONSHIPS, AND SYNAPSE DEVELOPMENT

There is considerable evidence for elimination of synapses and loss of neurons during development of the nervous system. Electrical activity in developing neural circuits induces functional and structural refin ement of many synaptic connections, but it is unclear whether the fund amental mechanism is one of strengthening appropriate synapses, combin ed with the regression of synapses that fail to become adequately stab ilized, versus a mechanism of elimination that specifically acts on in appropriate connections. A model of selective synapse elimination, bas ed on the activity-dependent release of proteases and glial-derived pr otease inhibitors, is presented and supported by evidence from an in v itro preparation of the mouse neuromuscular junction.