Seven investigators with career-long interest in the developmental biology of the synapse propose to extend their individual efforts by collaborations focused on the formation of synaptic connections and the degree to which synaptic connections change over time in adult animals. The work has five broad aims: (1) elucidating mechanisms that initiate axon growth and then terminate axon growth after synapses form; (2) identifying structures and molecules that influence the specificity of synaptic connections; (3) characterizing signals that promote the differentiation of synapses; (4) characterizing the molecular components of the postsynaptic membrane and the manner in which they are regulated; and (5) directly observing changes in identified synapses in adult animals over periods of weeks to months. We have chosen to carry out this work in vertebrates - generally mammals - because of our concern that the findings be applicable to the human nervous system and to human neurological disorders. The significance of this work lies in its potential contribution to the solution of one of the major problems confronting modern neurobiology: how the formation and malleability of synapses explain the remarkable adaptive abilities of the nervous system. Knowledge gained about normal development and plasticity of synapses will also advance our understanding of pathological situations in which synaptic connections fail to form properly or degenerate prematurely.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
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Washington University
Schools of Medicine
Saint Louis
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