Regulators of AWC-Mediated Olfactory Plasticity in Caenorhabditis elegans

Abstract

While most sensory neurons will adapt to prolonged stimulation by down-regulating their responsiveness to the signal, it is not clear which events initiate long-lasting sensory adaptation. Likewise, we are just beginning to understand how the physiology of the adapted cell is altered. Caenorhabditis elegans is inherently attracted to specific odors that are sensed by the paired AWC olfactory sensory neurons. The attraction diminishes if the animal experiences these odors for a prolonged period of time in the absence of food. The AWC neuron responds acutely to odor-exposure by closing calcium channels. While odortaxis requires a Gα subunit protein, cGMP-gated channels, and guanylyl cyclases, adaptation to prolonged odor exposure requires nuclear entry of the cGMP-dependent protein kinase, EGL-4. We asked which candidate members of the olfactory signal transduction pathway promote nuclear entry of EGL-4 and which molecules might induce long-term adaptation downstream of EGL-4 nuclear entry. We found that initiation of long-term adaptation, as assessed by nuclear entry of EGL-4, is dependent on G-protein mediated signaling but is independent of fluxes in calcium levels. We show that long-term adaptation requires polyunsaturated fatty acids (PUFAs) that may act on the transient receptor potential (TRP) channel type V OSM-9 downstream of EGL-4 nuclear entry. We also present evidence that high diacylglycerol (DAG) levels block long-term adaptation without affecting EGL-4 nuclear entry. Our analysis provides a model for the process of long-term adaptation that occurs within the AWC neuron of C. elegans: G-protein signaling initiates long-lasting olfactory adaptation by promoting the nuclear entry of EGL-4, and once EGL-4 has entered the nucleus, processes such as PUFA activation of the TRP channel OSM-9 may dampen the output of the AWC neuron. Caenorhabditis elegans is capable of sensing a variety of attractive volatile compounds. These odors are the worm's “best guesses” as to how to track down food. Employing calculated approximations underlies a foraging strategy that is open to failure. When C. elegans track an odor which proves unrewarding, they must modify their behavior based on this experience. They also need to prevent over-stimulating their neurons. To accomplish this, C. elegans olfactory sensory neurons adapt to odors after a sustained exposure to odor in the absence of food. Within the pair of primary odor-sensory neurons, termed the AWCs, adaptation requires the cGMP-dependent protein kinase G (PKG), EGL-4. Exposing animals to AWC–sensed odors for approximately 60 minutes results in a long-lasting (∼3 hour) adaptation that requires the nuclear translocation of EGL-4. To understand how sensory transduction and desensitization machinery converge to achieve olfactory adaptation, we asked whether odor-induced EGL-4 nuclear accumulation was affected by gene mutations that abrogate either odor sensation of or adaptation to AWC–sensed odors. We find that G-protein signaling represents the integration point where primary odor sensation and odor adaptation pathways diverge. PUFA signaling, calcium, and decreased diacylglycerol all dampen the response of the AWC neuron to odor downstream of this divergence.