Research
Animals in their natural environment perceive a wide variety of ecological cues and modify their behaviors based on their experiences. A central goal of neurobiology is to understand the function of neural circuits that regulate these dynamic behaviors. Our research focuses on olfactory learning and chemical signaling among species, and we employ the nematode Caenorhabditis elegans as a genetic and genomic model system to address these questions.
The C. elegans model system
A human brain contains billions of neurons and trillions of synapses. This complexity poses a formidable hurdle for a detailed understanding of its function. Because the development and function of the C. elegans nervous system share basic features with those of other animals, we can use C. elegans as a model system to address fundamental principles of neural circuit function. C. elegans senses a variety of odorants and water-soluble compounds through a well characterized chemosensory system. Its relatively simple nervous system contains 302 neurons and generates reliable and quantifiable behaviors. The well-defined cellular morphology and determinate neuronal connections of C. elegans allow for behaviors to be dissected at the level of individual neurons and circuits. Therefore, the C. elegans model offers unique strengths to integrate molecular genetic analysis with systems neuroscience to understand information flow and processing in neuronal networks.
C. elegans and its neuroanatomy:
Mechanisms of olfactory learning
Studies using other models suggest that neuromodulatory inputs modify olfaction during olfactory learning. Our laboratory is using the C. elegans olfactory system to pursue a detailed understanding of olfactory learning at the level of individual neurons.
As a free-living nematode that feeds on bacteria in soil, C. elegans can distinguish among different bacteria. Pathogenic bacteria are prominent environmental hazards and likely affect C. elegans’ survival. Our work has shown that C. elegans is capable of associative olfactory learning to avoid pathogenic bacteria. We identified a serotonergic circuit that converges with olfactory pathways and regulates this learning process. Pathogen exposure enhances serotonergic signaling in one pair of serotonergic neurons and increased serotonin signaling accelerates learning, probably by functioning as a negative-reinforcing cue. We hypothesize that serotonergic modulatory inputs modify the functions of olfactory neurons to change animal’s olfactory behaviors based on its experience with the training pathogen. This work identified a direct link between the learning behavior and a molecular change in a single pair of neurons.
We are using this system to address a fundamental question in the learning field: how neuromodulatory inputs shape the activity of neural circuits to regulate an animal’s responses to conditioned stimuli. Three related projects are underway to achieve a molecular understanding of this question at the level of individual neurons:
1. Identification of the olfactory learning circuit and the cellular
sites at which olfactory pathways converge with serotonergic
neuromodulatory inputs.
2. Characterization of mechanisms by which pathogen
exposure enhances serotonin signaling in the negative-
reinforcing pathway.
3. Characterization of mechanisms by which enhanced
serotonin signaling modifies the function of the olfactory
pathways.
Chemical recognition of bacteria by C. elegans
C. elegans lives in decomposing organic matter and soil, environments housing immense communities of microorganisms. It is estimated that one gram of soil around a plant root contains up to 10 million bacterial cells. In the laboratory, C. elegans feeds on benign bacteria, such as E. coli, that can support its development and reproduction. However, many soil-associated bacteria are pathogenic to C. elegans and likely affect nematode survival in the field.
It has been known for years that C. elegans is able to distinguish among different bacteria species, however, the mechanism of this recognition is largely unknown. Since C. elegans does not possess a visual or auditory system, the recognition of different bacteria species is presumably achieved through chemosensation. We have collaborated with the laboratory of Dr. Jonathan Ewbank (Universite de la Mediterranee, France) to identify a family of bacterially-produced natural products that are sensed by specific C. elegans chemosensory neurons. This work suggests possible mechanisms of bacterial species recognition by C. elegans in its natural environment.
Our lab is interested in further understanding chemical signaling between C. elegans and bacteria. We are combining behavioral analysis, nematode and bacterial genetics, and ecological analysis to understand the natural cues and neural circuits regulating species recognition.
Zhang Laboratory of Neuroethology
