Calcium dynamics regulating the timing of decision-making in C. elegans

Abstract

Brains regulate behavioral responses with distinct timings. Here we investigate the cellular and molecular mechanisms underlying the timing of decision-making during olfactory navigation in Caenorhabditis elegans. We find that, based on subtle changes in odor concentrations, the animals appear to choose the appropriate migratory direction from multiple trials as a form of behavioral decision-making. Through optophysiological, mathematical and genetic analyses of neural activity under virtual odor gradients, we further find that odor concentration information is temporally integrated for a decision by a gradual increase in intracellular calcium concentration ([Ca 2+ ] i ), which occurs via L-type voltage-gated calcium channels in a pair of olfactory neurons. In contrast, for a reflex-like behavioral response, [Ca 2+ ] i rapidly increases via multiple types of calcium channels in a pair of nociceptive neurons. Thus, the timing of neuronal responses is determined by cell type-dependent involvement of calcium channels, which may serve as a cellular basis for decision-making.

A hybrid versatile method for state estimation and feature extraction from the trajectory of animal behavior

“…elegans neurons in the presence of odor stimuli resembling those that the worms experience during the odor avoidance behavior in the plates (Fig. 7A) (Tanimoto et al, 2017). Using the OSB2 system, we found that ASH neurons are the major sensory neurons to cause pirouettes upon increases in 2-nonanone concentration (Tanimoto et al, 2017).…”

“…6D and E). Because the previous study demonstrated that worm odor avoidance behavior depends on dC rather than C at least in the naive condition (Tanimoto et al, 2017), one possibility is that the changes in the responsiveness of worms to dC is the underlying reason for the enhanced odor avoidance. However, it is also possible that the odor-experienced worms were somehow located farther away from the odor source than the unexperienced worms, and hence, sensed lower odor concentrations and shallower odor concentration change than the latter.…”

“…Calcium imaging of the worms' ASH neurons was performed according to the previous method with some modifications (Tanimoto et al, 2017). Briefly, transgenic strains expressing GCaMP3 (Tian et al, 2009) and mCherry (Shaner et al, 2004) in ASH sensory neurons under the sra-6…”

“…promoter (KDK70034 and KDK70072; 20 ng/µl of sra-6p::GCaMP3, 20 ng/µl of sra-6p::mCherry, 10 ng/µl of lin-44p::GFP, 50 ng/µl of PvuII-cut N2 genomic DNA as a carrier in N2 background) were placed on an NGM agar plate on a robotic microscope system, OSB2 (Tanimoto et al, 2017). Although these transgenic worms were immobilized with the acetylcholine receptor agonist levamisole (Lewis et al, 1980) for high-throughput data acquisition through simultaneous imaging of multiple worms, the previous study revealed that the ASH activity is essentially unaffected by levamisole-treatment (Tanimoto et al, 2017). A constant gas flow of 8 mm/min was delivered, in which the mixture rate of 2-nonanone gas with air was changed to create a temporal gradient of odor concentration.…”

“…As an example of comprehensive feature extraction from a behavioral state, we focused on learning-dependent changes in cluster 0 (run) because the values of their centroid migration are quantitatively more reliable than cluster 1 (pirouette) as mentioned above. In addition to the basic behavioral features used for the estimation of behavioral states (V, dV, B, and dB), we also calculated directedness (Dir) (Gorelik and Gautreau, 2014), and the odor concentration (C) and temporal change in odor concentration (dC) that each worm experienced during the odor avoidance behavior; C and dC were calculated based on actual measurements of the dynamic odor gradient (Tanimoto et al, 2017;Yamazoe-Umemoto et al, 2018). For these, we calculated the initiation (Ini), middle (Mid), termination (Ter), and all (All) values of a cluster 0 segment ( Fig.…”