Serotonergic neurons deploy a wide array of varicosities from which serotonin is thought to be released. A recent review summarizes some of this work. Our lab is interested in:
1) How the underlying branch structures for these neurons form
Below is an image from John Chen's work which looks at how the serotonergic neuronal branches form in the Drosophila larval CNS. Much work stills needs to be done to understand how these branches form. While the branches from different cells tile from one another, our evidence is against inter-cellular interaction.
2) Underlying structure of varicosities, their distribution and regulation
We have done some work on varicosity ultrastructure by immuno-EM. While we clearly need to do more work, what we have seen is very similar to previous studies of serotonergic varicosities in other insects and vertebrates.
We have found that serotonin regulates varisocity structure and are currently investigating the mechanism.
See commentary in Science News (http://www.sciencenews.org/view/feature/id/59408/title/A_pregnant_question)
We have also examined how varicosities are distributed in 3D space. The expectation was some regular array but we find a fractal-like clustered distribution that we are buring to understand.
3) Serotonergic function
In collaboration with Jill Venton's lab in the Chemistry department, we have used electrochemical methods to follow serotonin release in a single CNS ganglion. We plan to continue using this method to determine how the physiology of serotonin release relates to varicosity structure/deployment.
4) Serotonin levels and disease
Daubert, Elizabeth, Heffron, Dan, Mandell, James and Barry Condron. Elevated serotonin induces neuroprotective dystrophic neurites in Drosophila. MCN 2010 44:297-306. pdf See commentary in Science News (http://www.sciencenews.org/view/feature/id/59408/title/A_pregnant_question)
While serotonin regulates serotonergic geometry, we wondered what would happen if we generated a fly with excess serotonin. The result was the formation of large cell-body-sized swellings, which we term spheroids (a neuropathalogical term) on serotonergic branches. These are very similar in structure to those seen in mice treated with certain serotonin-acting drugs (see figure). Given certain conditions, we have found that challenge with high serotonin can be lethal and we are currently investigating the basis of this serotonin-toxicity.
5) Developing a new model system to study serotonergic function/future projects
Daubert, Elizabeth and Barry Condron. Serotonin regulates neuronal morphology and circuits. 2010 TINS In press. pdf
Below is from recent review:
We are currently developing a way of following the biological effects of serotonin on a sensory-motor circuit. The plan is to develop a model whereby we can manipulate serotonergic function, monitor these effects on serotonergic physiology, and then readout their results on a characterized circuit. With the quantitive data from the circuit analysis, we hope to develop a virtual ganglion in which we can simulate serotonergic and CNS function.