Neuronal analysis of value-based decision making in C. elegans

Decision making is a central function of the brain and the focus of intensive study in neuroscience, psychology, and economics. Value-based decision making (e.g., ‘which fragrance do you prefer?’ not 'which smells more like roses?') guides significant, sometimes life-changing, choices yet its neuronal basis is poorly understood. Research into this question would be accelerated by the introduction of genetically tractable invertebrates with small nervous systems, like the Drosophila and C. elegans. We have recently shown that the nematode C. elegans makes value-based decisions. This was done using a formal economic method – the Generalized Axiom of Revealed Preference (GARP). The basis of the method is to establish that the subject's choices are internally consistent with respect to transitivity (A > B > C ⇒ A > C). In the wild, C. elegans feeds on a variety of bacteria and learns to prefer the more nutritious species. We tested worms on a set of decisions between a high quality species and a low quality species at a range of relative concentrations and found the worm’s choices to be 100% transitive, the necessary and sufficient condition for value-based decision making. Further, we found that the olfactory neuron AWC, known to be activated by the sudden absence of food, is required for intact food choice behavior. Surprisingly, however, we found that AWC is also activated by the switch from high quality food to low quality food, even when the two foods are at the same concentration. Thus, food value may be represented at the level of individual olfactory neurons. We are now investigating the neural mechanisms of choice transitivity. C. elegans selects food sources utilizing klinotaxis, a chemotaxis strategy during locomotion in which the worm’s head bends more deeply on the side of preferred food. The chemosensory neurons, interneurons, and motor neurons of a candidate circuit for klinotaxis have been identified. Extrapolating from our findings with respect to AWC, we have developed a model of the circuit in which distinct chemosensory neuron types encode food quality and quantity during particular phases of head bending. Activation of downstream interneurons in the model is the weighted sum of these inputs in accordance with phase information. The model proposes that the signs and strengths of synaptic weights in the biological circuit are adjusted to ensure that subjective value is a monotonic function of the relative quantity of high and low quality food, a property that guarantees transitivity under GARP. Work in progress tests the model using calcium imaging, optogenetic activation, and ablations of each neuron in the circuit.