Previous studies have shown that the formation of early connections with targets and afferents plays an important role in regulating neuronal survival. The specific signals that mediate these target and afferent influences are of considerable interest. Recent studies suggest that synaptic transmission, post-synaptic activity, axonal branching and terminal contacts, and secreted neurotrophic molecules may all be used as signals to regulate the number of surviving neurons. We are attempting to understand the cellular and molecular events involved in each of these suspected regulatory processes. Attainment of this goal may help shed light on the reasons why neurons die pathologically later in life, as occurs in a variety of human neurodegenerative disorders, and may also aid in understanding the biological significance of this intriguing but still poorly understood phenomenon.
Neuronal death is only one of many critical steps in the construction of a nervous system.
The attainment of appropriate connections between neurons and their targets is another fundamental event that is of great interest to developmental neuroscientists. The emergence of adaptively appropriate behavioral patterns depends upon the formation of organized patterns of connectivity. We have been studying the formation of axonal pathways and synaptic connections by spinal cord neurons in the chick embryo that project within the central nervous system to spinal and brain targets. Our initial studies indicate that the pathways formed by the axons of these cells project unerringly in the appropriate locations and directions from the very onset of pathway formation. We are presently using in ovo and in vitro preparations for carrying out a variety of surgical, pharmacological and immunological perturbations to reveal the cellular, extracellular and molecular cues involved in pathway formation.