Abstract

A fundamental property of the nervous systems across the animal kingdom is the ability to select appropriate actions and sequences of actions in response to sensory cues. Many behaviors are physically mutually exclusive so commitment to one requires complete suppression of others. Further, because many behaviors are serially organized into sequences of actions, mechanisms must also exist that control transitions from one action to the next. The circuit mechanisms by which nervous systems achieve behavioral choice, stability and transitions are still incompletely understood. A key step in understanding these functions is to identify neurons and brain areas involved in controlling behavioral choice, stability and transitions. To do this, we developed an approach where we combined a large-scale neuronal inactivation screen with an automated action detection of sensorimotor decisions and sequences in response to a sensory cue. We characterized the response of wild-type larvae to a mechanosensory stimulus and found they can respond to the stimulus with a probabilistic sequence of 4 possible actions (head-cast, head-retraction, back-up and stop). We analyzed behaviors from around three hundred thousand larvae (N=2.9x105) where we selectively silenced small numbers of neuron types and individual neuron types systematically across the nervous system using a library of Drosophila GAL4 lines and determined the effect of these manipulations on larval mechanosensory responses. We identified neurons and brain-regions that when inactivated affected Drosophila larval sensorimotor decisions and sequence transitions between the different actions. Specifically, we identified 51 candidate lines for sensory processing and 24 candidate lines for competitive interactions. We also detected phenotype categories for sequence transitions consistent with a model of sequence generation where transitions and reversals are independently controlled. These findings provide the basis for understanding how sensorimotor decisions and sequence transition are controlled by the nervous system.