Neuropeptide-Driven Cross-Modal Plasticity following Sensory Loss in Caenorhabditis elegans
Ithai Rabinowitch, Patrick Laurent, Buyun Zhao, Denise Walker, Isabel Beets, Liliane Schoofs, Jihong Bai, William R. Schafer, Millet Treinin
Published: January 08, 2016
Abstract
Sensory loss induces cross-modal plasticity, often resulting in altered performance in remaining sensory modalities. Whereas much is known about the macroscopic mechanisms underlying cross-modal plasticity, only scant information exists about its cellular and molecular underpinnings. We found that Caenorhabditis elegans nematodes deprived of a sense of body touch exhibit various changes in behavior, associated with other unimpaired senses. We focused on one such behavioral alteration, enhanced odor sensation, and sought to reveal the neuronal and molecular mechanisms that translate mechanosensory loss into improved olfactory acuity. To this end, we analyzed in mechanosensory mutants food-dependent locomotion patterns that are associated with olfactory responses and found changes that are consistent with enhanced olfaction. The altered locomotion could be reversed in adults by optogenetic stimulation of the touch receptor (mechanosensory) neurons. Furthermore, we revealed that the enhanced odor response is related to a strengthening of inhibitory AWC→AIY synaptic transmission in the olfactory circuit. Consistently, inserting in this circuit an engineered electrical synapse that diminishes AWC inhibition of AIY counteracted the locomotion changes in touch-deficient mutants. We found that this cross-modal signaling between the mechanosensory and olfactory circuits is mediated by neuropeptides, one of which we identified as FLP-20. Our results indicate that under normal function, ongoing touch receptor neuron activation evokes FLP-20 release, suppressing synaptic communication and thus dampening odor sensation. In contrast, in the absence of mechanosensory input, FLP-20 signaling is reduced, synaptic suppression is released, and this enables enhanced olfactory acuity; these changes are long lasting and do not represent ongoing modulation, as revealed by optogenetic experiments. Our work adds to a growing literature on the roles of neuropeptides in cross-modal signaling, by showing how activity-dependent neuropeptide signaling leads to specific cross-modal plastic changes in neural circuit connectivity, enhancing sensory performance.
Author Summary
The brain has the remarkable capacity to respond to sensory loss by boosting remaining functioning senses. For example, certain features of hearing are improved in blind people. What are the cellular and molecular mechanisms underlying this effect? How is a certain sense strengthened? If it is possible to hear better, why don’t we hear better in the first place? To simplify these problems, we examined them in an organism with a substantially less complicated nervous system than our own, the roundworm C. elegans. We discovered that C. elegans mutants that cannot sense touch to the body exhibit an improved sense of smell. We were able to pinpoint this change in sensory performance to a change in strength of a specific synapse in the olfactory circuit. We further found that in normal worms, this olfactory synapse is suppressed through a neuropeptide signal transmitted from the touch sensing neurons. In contrast, without any touch input, the touch neurons secrete less neuropeptide, the olfactory synapse becomes stronger, and the sense of smell improves. We were able to reverse these effects by artificially stimulating the touch neurons and by engineering a new synapse into the olfactory circuit.
Citation: Rabinowitch I, Laurent P, Zhao B, Walker D, Beets I, Schoofs L, et al. (2016) Neuropeptide-Driven Cross-Modal Plasticity following Sensory Loss in Caenorhabditis elegans. PLoS Biol 14(1): e1002348. doi:10.1371/journal.pbio.1002348
Academic Editor: Piali Sengupta, Brandeis, UNITED STATES
Received: August 20, 2015; Accepted: December 3, 2015; Published: January 8, 2016
Copyright: © 2016 Rabinowitch et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Data Availability: All relevant data are within the paper and its Supporting Information files.
Funding: IR was supported by postdoctoral fellowships granted by the Israeli Science Foundation Bikura program, the Edmond and Lily Safra Center for Brain Sciences (ELSC), and the Institute for Medical Research Israel-Canada (IMRIC). PL is Research Associate of the “Fond National de la Recherche Scientifique” (FNRS). BZ was supported by the Medical Research Council and the EMBO Fellowships Programme. IB was supported by a postdoctoral fellowship of the Research Foundation-Flanders (FWO). Work done in the LS lab was funded by European Research Council Grant ERC-2013-ADG-340318. Work done in the JB lab was funded by FHCRC New Development Grant, and NIH grant NINDS R01NS085214. Work done in the WRS lab was funded by MRC grant MC-A022-5PB91 and Wellcome Trust Investigator Award WT103784MA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Abbreviations: AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; ATR, all-trans retinal; BSA, bovine serum albumin; Bz, benzaldehyde; CHO, Chinese hamster ovary; ChR2, Channelrhodopsin2; DA, diacetyl; IAA, isoamyl alcohol; INS-1, insulin-like peptide transgene; Mec, mechanosensory; MosSCI, Mos1 single-copy insertion; Py, pyrazine; SEM, standard error of the mean; TRN, touch receptor neuron
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