| Popis: |
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 C. elegans. 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 Gαq-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 nlp- 1, nlp-14 and nlp-18 from axons of the two ASI sensory neurons and both Gαq and Gαs 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 nlp-1 activate NPR-11 on the AIA and AIY interneurons and neuropeptides encoded by nlp-14 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. |
