Our Work
Serotonin neurons regulate many behavioral functions such as mood, appetite, sleep, and cognition. Abnormalities in the morphology of these neurons have recently been implicated as contributing factors in behavioral disorders, yet the cellular mechanisms underlying these abnormalities are unclear. The powerful genetic tools available in Drosophila allow us to manipulate cellular and molecular function of these specific neurons during development. Together with a variety of emerging techniques such as Brainbow circuit analysis, Expansion Microscopy, live-cell imaging, and behavioral assays, we seek to understand how abnormalities in the serotonin system arise at the intracellular, anatomical, and behavioral levels.
01
SEROTONIN RECEPTOR 1A AUTOCRINE SIGNALING
In vitro cellular analysis
5-HT1A couples to a variety of intracellular signaling pathways and mechanisms depending on cell type, neuronal activity, and developmental time. While there have been many studies on 5-HT1A signaling, very few of these have been in true serotonergic neurons. We are using a primary serotonergic neuron culture system to more develop clearer understanding of the mechanism of 5-HT1A autocrine signaling at varying developmental stages.
02
SEROTONIN AUTOREGULATION OF SEROTONERGIC AXON MORPHOLOGY
In vivo circuit analysis
In addition to its established role as a neurotransmitter, serotonin signaling via autoreceptors is believed to affect axon branch morphology during development. We are currently using genetic and pharmacological methods to tune serotonin levels during development. Doing so in Brainbow flies will allow us to reconstruct how these manipulations affect the final morphology of serotonergic axons.
03
THE ROLE OF SEROTONIN AUTORECEPTORS IN SEROTONERGIC SYSTEM FUNCTION
Behavior assays
Our ongoing work describes unique roles for serotonin receptors expressed in serotonergic neuron, deemed autoreceptors, compared to non-serotonergic neurons. Using RNAi of serotonin autoreceptors, we are currently screening a variety of behaviors at the larval and adult stages. These include, but are not limited to, locomotion, feeding, and phototaxis.
04
MECHANISMS OF HALLUCINOGEN TREATMENTS FOR MENTAL HEALTH DISORDERS
Drosophila as a model system
Hallucinogens such as LSD are promising treatments for a variety of severe mental health conditions such as Major Depressive Disorder (MDD), which is correlated with increased expression of 5-HT2A. We are currently developing Drosophila as a model system with which to mimic the genetic and behavioral aspects of MDD with the intent of testing the effects of the 5-HT2A agonist LSD on the genetic profiles, behavior, and physiology across different clinically relevant dosing paradigms.
