Here, by applying systematic single-cell ablation analysis to the C. elegans wiring diagram, we mapped the functional organization of a neural network from sensory input to motor output that regulates the aversive olfactory learning of C. elegans on pathogenic bacteria. This type of learning appears similar to the Garcia’s effect, a common form of learning that animals learn to avoid the taste or smell of a food that makes them ill ( Garcia et al., 1955). To our knowledge, our work presents the first systematic analysis on the cellular basis for similar types of learning. We have found that two different neural circuits are required Vemurafenib order for C. elegans to generate its naive and

trained olfactory preferences. The AWB-AWC sensorimotor circuit is required for animals to display their naive olfactory preference, whereas the ADF modulatory circuit is specifically needed for the animals to modify the naive olfactory preference

after training. Both circuits are connected to downstream motor neurons that control turning rate, suggesting that they regulate motor output during the behavioral display of olfactory preference in either naive or trained animals (Figures 5H and 6H). Furthermore, calcium imaging responses of AWB and AWC olfactory sensory neurons in naive animals are consistent with the behavioral olfactory preference for the smell of PA14 over the smell of OP50. Switching from OP50-conditioned medium to PA14-conditioned medium inhibited intracellular calcium dynamics in AWC and stimulated AWB (Figures click here 5A, 5D, S4A, and S4C). The differential effects of OP50 and PA14 stimuli on the activity of these olfactory sensory neurons are likely to be encoded in the intrinsic properties of the neurons, such as expression of a particular group of G protein coupled receptors. The differential response of these olfactory sensory neurons propagates through downstream neurons to produce different turning rates depending on olfactory

inputs (Figure 5H). Our results on olfactory tuclazepam sensory neurons in the learning network suggest that intrinsic neuronal responses of olfactory sensory neurons directly regulate the behavioral olfactory preference of naive animals. Interestingly, the olfactory response of AWB and AWC sensory neurons to the smells of benign and pathogenic bacteria were not changed by training (Figures 6A, 6D, S4B, and S4D). The contrast between the behavioral aversion to PA14 and the neuronal preference of sensory neurons to PA14 in trained animals suggests training-dependent alterations to signal transduction to the downstream of the olfactory learning network. This hypothesis is consistent with our analyses on the turning rate of trained animals, which indicate that aversive experience increases the turning rate toward the training bacterium PA14 through RIA interneurons and SMD motors neurons.