A pivotal issue in developmental neuroscience pertains to the mechanisms regulating the choice of the correct target by a nerve cell. This issue will be addressed by examining the embryonic assembly of a functional neural circuit in the medicinal leech, Hirudo medicinalis. The stereotyped adult circuitry of the leech heart excitor motor neurons that drive precisely coordinated rhythmic contractions of the heart tubes is particularly well understood. However, this stereotyped circuitry arises as result of initial axonal projections to several target regions followed by a retraction of the incorrectly positioned axons. The processes of initial outgrowth and later retraction of these axons will be investigated using light, laser and electron microscopic visualization, as well as intracellular electrophysiology. Parallel experiments will determine the developmental time course of functional synaptic connectivity between central interneurons that ultimately drive the coordinated behavior and the heart excitor neurons. The simplicity of this system will allow exploration across several levels of analysis, from morphology to behavior, of the developmental interactions that occur during the assembly of a simple, but behaviorally relevant neural circuit. It is expected that an understanding of the principles that underlie the development of specificity in this system will pertain to more complex systems, since the developmental strategy of initial axonal exuberant growth followed by retraction is commonly used by embryonic neurons in higher species as well.
