Animals' sensory systems adjust their responsiveness to environmental stimuli that vary greatly in their intensity. Here we report the neural mechanism of experience-dependent sensory adjustment, especially gain control, in the ASH nociceptive neurons in Caenorhabditis elegans. Using calcium imaging under gradual changes in stimulus intensity, we find that the ASH neurons of naive animals respond to concentration increases in a repulsive odor 2-nonanone regardless of the magnitude of the concentration increase. However, after preexposure to the odor, the ASH neurons exhibit significantly weak responses to a small gradual increase in odor concentration while their responses to a large gradual increase remain strong. Thus, preexposure changes the slope of stimulus-response relationships (i.e., gain control). Behavioral analysis suggests that this gain control contributes to the preexposure-dependent enhancement of odor avoidance behavior. Mathematical analysis reveals that the ASH response consists of fast and slow components, and that the fast component is specifically suppressed by preexposure for the gain control. In addition, genetic analysis suggests that G protein signaling is required for the fast component. Thus, our integrative study demonstrates how prior experience dynamically modulates stimulus-response relationships in sensory neurons, eventually leading to adaptive modulation of behavior.

Calcium imaging of ASH sensory neurons was performed as previously reported (Tanimoto et al., 2017; Tanimoto and Kimura, 2021). In brief, transgenic lines expressing GCaMP3 and mCherry in ASH were placed on NGM plates and observed under our original microscope system, OSB2. To measure the neural activity of multiple animals in a single observation, the transgenic animals were immobilized using levamisole, an agonist to the acetylcholine receptor (Lewis et al., 1980); ASH response is not affected by levamisole treatment (Tanimoto et al., 2017).

For odor stimulation, we delivered a mixture of 2-nonanone and air at a total of 8 mm/min and created a temporal changing gradient of odor concentration by changing the ratio of 2-nonanone to air. We measured the gradients using a custom-made semiconductor sensor before and after performing the calcium imaging experiments on each day (Tanimoto and Kimura, 2021).

We divided the fluorescent signals of GCaMP3 and mCherry through a dual-wavelength measurement optical system, w-view (Hamamatsu Photonics), and captured their fluorescence images using an EM-CCD camera (ImagEM, Hamamatsu Photonics). After subtracting the background, we extracted the fluorescence intensity of the cell body using ImageJ and used their ratio (GCaMP/mCherry) as the data.