Michael R Koelle
Yale University, CT·Neuroscience
Brain disorders such as mood disorders and Parkinson's disease appear to involve faulty signaling by neuromodulators. These chemicals, such as serotonin, tune how groups of neurons behave.
- Fields
Neuroscience
Genetics
Biochemistry
- Topics
C. elegans
Caenorhabditis elegans
egg-laying circuit
- Grants
- 1 known grant, through Dec 2028
What they work on
- Test whether Gαo, a G protein that relays inhibitory signals, turns off egg-laying neurons and muscles in C. elegans. It may do so by activating a GTPase activator and a diacylglycerol kinase that end Gαq signaling. Approaches include biochemistry, genetics, calcium imaging and electrophysiology.
- Define the structure and function of the remaining uncharacterized parts of the egg-laying circuit, including PVW neurons and gap junctions between muscle cells, using genetics, calcium imaging and electron microscopy.
- Determine how mechanosensory feedback switches the circuit off after eggs are laid, including neurons that detect egg release and muscles that sense remaining eggs, using genetics, calcium imaging and physiological approaches.
More about the research
Yet it is hard to understand these diseases without knowing how a whole neural circuit works. This project takes a deep approach: map every signaling event in one simple circuit. The circuit controls egg laying in the tiny worm C. elegans, which uses the same types of neuromodulators as the human brain. The circuit switches between roughly 20-minute inactive periods, while eggs build up in the uterus, and roughly 2.5-minute active periods, when eggs are laid. Earlier work studied how the circuit turns on. This project asks how it turns off.
Why it matters
Neuromodulators like serotonin are implicated in mood disorders, Parkinson's disease and other brain conditions. Yet how they shape whole-circuit activity is poorly understood. Mapping every signaling event in a simple worm circuit could reveal shared principles of how neural circuits switch on and off. These principles could improve understanding of how faulty neuromodulator signaling contributes to human brain disorders.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Jagan Srinivasan
Worcester Polytechnic Institute, MA·Neuroscience
Define how NLP-3 neuropeptides drive hermaphrodite avoidance of the pheromone ascaroside-8 in C. elegans, using CRISPR mutants, rescue with synthetic peptides, and quantitative behavioral assays.
Mark Alkema
University of Massachusetts Chan Medical School, MA·Neuroscience
Identify the neuronal targets and molecular pathways through which nitric oxide made by gut bacteria suppresses seizures in C. elegans unc-2/CaV2α gain-of-function mutants, a worm model of a migraine-linked calcium channel disorder.
Adema Ribic
University of Virginia, VA·Neuroscience
Determine how premature birth alters synchronous intrinsic activity, the coordinated spontaneous firing of neurons, in the neonatal mouse prefrontal cortex using in vivo electrophysiology in preterm mice born one day early.
The school
Yale University: 73 labs on PI Pages, $1.5B a year on research, 438 research doctorates a year.
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