Serotonin neurons are relatively few in number in the CNS but they modulate a multiplicity of behaviors and physiological processes. To achieve their neuromodulatory role, serotonergic neurons elaborate a complex network of arbors that form the most expansive neurochemical system in the brain (Jacobs and Azmitia, 1992). These arbors target specific regions of the nervous system, where they form extrasynaptic neurosecretory terminals (herein termed ENTs). It is not understood how the specificity of neurosecretory terminals, which lack distinct post-synaptic partners, is achieved.
Serotonergic pathways, ranging from neurotransmitter biogenesis to signaling, are well conserved across evolution. Nematodes, like vertebrates, have only a handful of neurons that produce serotonin, and these neurons exhibit morphological features similar to those seen in vertebrate serotonergic neurons. For instance, the main serotonergic neuron in C. elegans, called NSM, elaborates axonal arbors within a precise neuroanatomical coordinate overlying the nerve ring (Axang et al., 2008). We recently developed a system that allows us to assay NSM morphogenesis and synaptogenesis in vivo, in real time and with single cell resolution. This gives us an unprecedented opportunity to dissect the cellular and molecular mechanisms that regulate serotonergic synapse development in vivo. To identify how precise targeting is achieved in serotonergic neurons in vivo, we are working toward the following 3 goals:
1. How do ENT-containing arbors form with SPATIAL specificity in the nematode?
2. How is the TEMPORAL specificity of arborization and ENT formation regulated in the nematode?
3. What are the molecular mechanisms that contribute to the physical assembly and plasticity of ENTs and associated arbors?