The TRPV Channel OSM-9 is Required for Sleep-Dependent Olfactory Memory and is Expressed in Sensory Neurons That Do Not Promote Butanone Attraction

Abstract

AbstractMemory, defined as an alteration in behavior that follows as a consequence of experience, can form when a sensory stimulus is encountered at the same time that the animal experiences a negative or positive internal state. How this coincident detection of external and internal stimuli stably alters responses to the external stimulus is still not fully understood, especially in the context of an intact animal. One barrier to understanding how an intact biological circuit changes is knowing what molecular processes are required to establish and maintain the memory. The optically accessible and compact nervous system of C. elegans provides a unique opportunity to examine the molecular and cellular processes that promote memory formation. The C. elegans nematode can remember an odor such as butanone when it is paired with a single negative experience and the transient receptor potential (TRP) OSM-9/TRPV5/TRPV6 channel is known to be required for this memory. The multiple gating mechanisms of TRPV channels give them the potential to be the coincidence detectors required to integrate internal state and external stimuli. Here, we report that this TRPV channel is also required for acquisition and possibly consolidation of sleep-dependent, long-term memory of butanone. Using an endogenous CRISPR-based tag, we find that OSM-9 is expressed in the paired AWA olfactory neurons, the ASH nociceptive neuron pair, the mechanosensory OLQ tetrad, and the paired ADF and ADL sensory neurons. In these cells, OSM-9 protein is concentrated in the sensory endings, dendrites, and cell bodies, but excluded from the neurites in the nerve ring. In the tail, OSM-9 is expressed in the nociceptive phasmid neurons PHA and PHB, possibly PQR as well as PVP. In the midbody, it is possibly expressed in the mechanosensitive PVD neuron. Because OSM-9 is expressed in sensory neurons that do not participate in butanone chemosensory behavior, this indicates that cells extrinsic to the primary sensory circuit may participate in acquiring and consolidating memory.Author summaryHow organisms learn from their environment and keep these memories for the long term ensures their survival. There is much known about the regions of the brain and the various proteins that are essential for memory, yet the exact molecular mechanisms and dynamics required are not known. We aimed to understand the genetics that underlie memory formation. We tested a gene that encodes a transient potential receptor channel vanilloid channel, which is similar to the channels we have that sense spicy foods and other harmful cues. Our studies have shown that this gene is required specifically to acquire and perhaps consolidate memory. This protein is not expressed in the sensory neurons that respond to odor or in other downstream interneurons in this circuit, but it is expressed and possibly acts in a distinct set of sensory neurons. This indicates that long-term memory involves a wider array of sensory neurons than is required for the primary sensation. These channels are also implicated in neurological disorders where memory is affected, including Alzheimer’s disease. Thus, understanding how a circuit of sensory neurons memory formation involves a circuit could also help us learn how to treat these disorders.