GSBS Dissertations and Theses

ORCID ID

0000-0001-9613-5652

Approval Date

12-14-2016

Document Type

Doctoral Dissertation

Academic Program

Neuroscience

Department

Neurobiology; Francis Lab

First Thesis Advisor

Michael Francis, PhD

Keywords

C. elegans, Neuromodulation, Behavior, Neuropeptide signaling

Abstract

Neuropeptide signaling play critical roles in maintaining distinct behavioral states and orchestrating transitions between them. However, elucidating the mechanisms underlying neuropeptide modulation of neural circuits in vivo remains a major challenge. The nematode Caenorhabditis elegans serves as an excellent model organism to study neuropeptide signaling mechanisms encoded in relatively simple neural circuits. We have used the C. elegans egg-laying circuit as a model to understand how neuropeptide signaling modifies circuit activity to generate opposing behavioral outcomes. C. elegans egg-laying behavior is composed of alternating cycles of two states – short bursts of egg deposition (active phases) and prolonged periods of quiescence (inactive phases). We have identified two neuropeptides (NLP-7 and FLP-11) that are locally released from a group of neurosecretory cells (uv1) and coordinate the temporal organization of egglaying by prolonging the duration of inactive phases. These neuropeptides regulate activity within the core circuit by inhibiting serotonergic transmission between its individual components (HSN motorneurons and Vm2 vulval muscles). This inhibition is achieved at least in part, by reducing synaptic vesicle abundance in the HSN synaptic regions. To identify potential downstream signaling components that mediate the actions of these neuropeptides, we have performed a forward genetic screen and have identified a strong candidate. In addition, we are trying to identify the receptor(s) of these neuropeptides by using a candidate gene approach. Together, we demonstrate that local neuropeptide signaling maintains the periodicity of distinct behavioral states by regulating serotonergic transmission in the core neural circuit.

Comments

This dissertation includes 3 movies that are available under "Additional Files."

DOI

10.13028/M2B609

Rights and Permissions

Licensed under a Creative Commons license

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

Movie II-1.mp4 (921 kB)
Movie II-1. uv1 photostimulation in control animals

Movie II-2.mp4 (653 kB)
Movie II-2. uv1 photostimulation in nlp-7(lf);flp-11(lf) double mutants

Movie II-3.mov (918 kB)
Movie II-3. HSN photostimulation

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