Abstract
Many neurons release classical transmitters together with neuropeptide cotransmitters whose functions are incompletely understood. Here we define the relationship between two transmitters in the olfactory system of Caenorhabditis elegans, showing that a neuropeptide-to-neuropeptide feedback loop alters sensory dynamics in primary olfactory neurons. The AWC olfactory neuron is glutamatergic and also expresses the peptide NLP-1. nlp-1 mutants have increased AWC-dependent behaviors, suggesting that NLP-1 limits the normal response. The receptor for NLP-1 is the G protein-coupled receptor NPR-11, which acts in postsynaptic AIA interneurons. Feedback from AIA interneurons modulates odor-evoked calcium dynamics in AWC olfactory neurons and requires INS-1, a neuropeptide released from AIA. The neuropeptide feedback loop dampens behavioral responses to odors on short and long timescales. Our results point to neuronal dynamics as a site of behavioral regulation and reveal the ability of neuropeptide feedback to remodel sensory networks on multiple timescales.
Highlights
Many neurons release classical transmitters together with neuropeptide cotransmitters whose functions are incompletely understood
We found that npr-11 null mutants, like nlp-1 mutants, had increased turning during AWC-dependent local search behavior (Fig. 1c, Supplementary Table 1)
The npr-11 behavioral defect in local search behavior resembled the defect after AIA interneurons are killed with a laser[9], and the npr-11 defect was fully rescued by transgenic npr-11 expression in AIA interneurons under the gcy-28.d promoter (Fig. 1c). These results suggest that NLP-1 release from AWC activates the NPR-11 G protein-coupled receptors (GPCRs) on AIA
Summary
Many neurons release classical transmitters together with neuropeptide cotransmitters whose functions are incompletely understood. The relationships between sensory inputs, neuronal activity, and specific behavioral programs are unclear[2, 3] We are exploring these issues within a circuit that generates undirected search when animals are removed from food, and directed chemotaxis in odor gradients[4,5,6]. Double mutants between nlp-1 and eat-4, glr-1, or glc-3 had reduced turning rates, resembling the mutants that affected glutamate signaling (Fig. 1b) This result suggests that NLP-1 functions as a cotransmitter whose effects are only apparent when the classical transmitter glutamate is released: glutamate from AWC stimulates turning, and NLP-1 from AWC decreases the magnitude of this effect
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