MOLECULAR EFFECTS OF EARLY EXPERIENCE ON MOTOR NEURON

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During critical periods in neural development, the structure and function of the CNS can be profoundly influenced by an organism's interactions with its environment. In cats for example, the formation of normal lamination patterns in the dorsal lateral geniculate nucleus (LGN) and of ocular dominance columns in the striate cortex require normal early visual experience. In addition to anatomical and physiological changes, molecular characteristics of neurons are also sensitive to early visual experience. Monoclonal antibody Cat-301 recognizes an antigen on LGN Y-cells whose expression is tied to normal visual experience early in life. Monocular lid suture at birth not only inhibits the physiological and morphological development of Y- cells in the deprived layers of the LGN, but also the expression of the Cat-301 antigen on the same cells. After the critical period, monocular lid suture does not effect Y-cell morphology or physiology and likewise the Cat-301 antigen is unaffected. These findings suggest that the expression of the Cat-301 antigen provides a positive molecular marker for critical period events in visual system development. Our recent work indicates that Cat-301 is expressed on spinal cord motor neurons of hamsters in an experience-dependent manner. Just as Cat-301 expression on Y-cells is tied to normal early visual experience, its expression on hamster motor neurons is tied to normal neuromuscular experience in early life. Manipulating the neuromuscular environment in maturity has no effect on Cat-301 expression, indicating that its expression is not simply activity-dependent. Here we propose studies using the hamster spinal cord system to study experience-dependent features of development. This system presents many advantages for studying the neural activity that contributes to normal development as the motor unit is amenable to pharmacologic dissection, ultrastructural analysis and in vitro manipulation. Pharmacological studies will test the contribution of the components of the motor unit to development using a-bungarotoxin, colchicine and tetrodotoxin. EM studies will correlate ultrastructural events in synaptogenesis with Cat- 301 expression and critical period phenomena. A motor neuron culture system will be developed to confirm and extend this analysis. Finally, since Cat-301 is expressed on human motor neurons, we will attempt to define a developmental critical period for human motor neurons by assaying Cat-301 expression in human autopsy material of various ages. These studies are designed to increase our understanding of experience-dependent development. This knowledge may have important implications for functional recovery after injury in the developing and adult human CNS.