Neurons in many central nervous system (CNS) regions undergo a period of activity-dependent development that gives rise to morphological and electrophysiological properties that persist for the life of the animal. Using a monoclonal antibody directed against a unique cell surface proteoglycan, we have provided molecular evidence that hamster motor neurons exhibit activity-dependent development during a critical period in early postnatal life. Moreover, motor neuron development, like visual system development, is influenced by NMDA receptor activation. These studies show that activity-dependent development is reflected in the expression of specific molecules and that NMDA receptor mediated events can be studied quantitatively in motor neurons. Here we propose to: (1) investigate the role of target (muscle) function in activity-dependent development; (2) examine the role of motor neuron activity in the maturation of synaptic ultrastructure; (3) examine in adults the molecular and morphological consequences of neonatal NMDA receptor blockade; and (4) examine the developmental regulation of spinal cord NMDA receptor density and distribution. The immediate goal of these studies is an anatomic and molecular description of activity-dependent development at the single cell level. The long range goal is an understanding of the developmental events that regulate or limit the plasticity of the CNS.
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