Neuropeptides Amplify and Focus the Monoaminergic Inhibition of Nociception in <i>Caenorhabditis elegans</i>

Nutritional status can dramatically modulate olfaction and nociception. To better understand how food availability modulates olfactory responses, we examined the nutritionally-dependent, tyraminergic inhibition of aversive behavior mediated by the two nociceptive ASH sensory neurons in <i>C. elegans</i>. Tyramine (TA) and octopamine (OA) activate adrenergic-like signaling in invertebrates and are released during starvation. TA is released both synaptically and humorally and abolishes the food or 5-HT stimulation of ASH-mediated aversive responses through the Gα_q-coupled TA receptor, TYRA-3. TA and TYRA-3 stimulate the release of a complex mix of “inhibitory” monoamines, including OA and dopamine (DA), and neuropeptides from an array of additional neurons. For example, TYRA-3 stimulates the release of neuropeptides encoded by <i>nlp- 1</i>, <i>nlp-14</i> and <i>nlp-18</i> from axons of the two ASI sensory neurons and both Gα_q and Gα_s signaling in the ASIs are required for TA inhibition. The ASI neuropeptides required for TA inhibition are distinct from the ASI neuropeptides required for OA inhibition, suggesting that individual monoamines can stimulate the release of distinct subsets of ASI neuropeptides. The ASI neuropeptides activate receptors on downstream post-synaptic partners of the ASIs located throughout the sensory-mediated locomotory circuit. For example, neuropeptides encoded by <i>nlp-1</i> activate NPR-11 on the AIA and AIY interneurons and neuropeptides encoded by <i>nlp-14</i> activate NPR-10 on the ADL and ASK sensory neurons, suggesting that ASI peptidergic signaling is largely synaptic (or perisynaptic), in contrast to tyraminergic signaling that appears to be humoral. Together, these studies highlight the complexity of TA inhibition, with TA activating widespread global signaling cascades, and suggest that signaling from a complex “humoral soup” of monoamines is amplified and focused by the more localized synaptic (perisynaptic) release of neuropeptides to define nutritional state in the modulation of a wide variety of behaviors, including sensory-mediated locomotory decision-making. On a more general level, these studies emphasize the potential for neuropeptides to focus the more widespread monoaminergic activation involved in resetting complex neuronal circuits in all organisms.

Name thesis:degree_name

Doctor of Philosophy

Level thesis:degree_level

doctoral

Discipline thesis:degree_discipline

Biology (Cell-Molecular Biology)

Grantor dc:publisher

University of Toledo

Year dc:date

2013

Author dc:creator

• Hapiak, Vera M.

Contributors dc:contributor

• Komuniecki, Richard

• Neurobiology
• neuropeptides monoamines nociception nutritional modulation

Statement dc:rights

• unrestricted
• This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.

Language dc:language

English

Repository record dc:identifier

http://rave.ohiolink.edu/etdc/view?acc_num=toledo1357164473

OAI identifier oai:identifier

oai:etd.ohiolink.edu:toledo1357164473