Neural Cell Adhesion Genes in Synaptic Specificity

The synaptic connections in our brain form circuits that control all mental activity and behavior. How these connections are specified during brain development and function is largely unknown. The problem is difficult to study in humans or model mammals because the synaptic connections in the large brains of these species cannot currently be determined. Some mental illnesses may be due to abnormalities in synaptic connectivity?the inability to address this possibility in the absence of known connectivity is a major barrier to understanding such diseases. This study focusses on specification of synaptic connectivity in the only animal where detailed maps of synaptic connections are available. In the nematode worm, Caenorhabditis elegans, the wiring diagram, or connectome, of the entire nervous system has been determined. The C. elegans genome contains a similar set of neural cell adhesion genes thought to specify connectivity as humans. The function of these and additional genes will be studied in a neural network in the male. The expression patterns of neural cell adhesion genes in the neural network has been determined. The function of multiple neural cell adhesion genes in specification of a particular synaptic connection will be examined in detail in genetic and molecular studies. The binding properties of neural cell adhesion proteins involved in synapse formation will be determined in biochemical studies. The complement of neural cell adhesion genes that specify different connections will be compared and their activities in ectopic contexts will be examined. The aim is to uncover the molecular determinants of connectivity in the network. The results will allow studies in higher animals to focus on genes with known functions in defining neural circuits.