Identifying neural substrates of competitive interactions and sequence transitions during mechanosensory responses in Drosophila

Nervous systems have the ability to select appropriate actions and action sequences in response to sensory cues. The circuit mechanisms by which nervous systems achieve choice, stability and transitions between behaviors are still incompletely understood. To identify neurons and brain areas involved in controlling these processes, we combined a large-scale neuronal inactivation screen with automated action detection in response to a mechanosensory cue in Drosophila larva. We analyzed behaviors from 2.9x10(5) larvae and identified 66 candidate lines for mechanosensory responses out of which 25 for competitive interactions between actions. We further characterize in detail the neurons in these lines and analyzed their connectivity using electron microscopy. We found the neurons in the mechanosensory network are located in different regions of the nervous system consistent with a distributed model of sensorimotor decision-making. These findings provide the basis for understanding how selection and transition between behaviors are controlled by the nervous system. Author summary All animals are constantly confronted with multiple behavioral options that they need to choose from in response to various stimuli. Yet how the brain controls the sensorimotor decision-making process and ensures that appropriate actions are chosen and correctly ordered remains a mystery. This is largely due to the difficulty in establishing causal relationships between neurons and sensorimotor decisions and determining the connectivity between the neurons underlying sensorimotor decisions. In this study, we used automated action detection to analyze behaviors of hundreds of thousands of Drosophila larvae in which we systematically silenced small subsets of neurons in response to a mechanosensory cue and identified candidate neurons for competitive interactions and transitions between different actions. We further analyzed the connectivity between these neurons using electron microscopy reconstruction and identified a putative network underlying sensorimotor decision-making during mechanosensory responses. We found this mechanosensory network is distributed in the nervous system from the first order interneuron on the sensory side to the motor side and higher order brain regions.