Circuits for bilateral looming feature integration in Drosophila
Authors:   , Jang HyoJong , von Reyn Catherine R. 
Published: August 2022

Animals must generate relevant behaviors in response to their rapidly changing environment that are essential for survival. To accomplish this goal, an animal's brain must acquire and process sensory input from the environment and then integrate this information to select and drive an appropriate behavior. However, the underlying mechanisms behind these sensory to motor transformations are not well understood as the neural circuits that bridge complex sensory inputs and relevant behavior outputs are largely incomplete. We use the fruit fly Drosophila melanogaster as our model organism to investigate sensorimotor transformations. In doing so we have great leverage to study underlying mechanisms at the level of individual neurons and small neural circuits. Approximately 60% of genes in humans have a homolog in the fly and many cellular mechanisms are well conserved. Additionally although the fruit fly has numerical simplicity in the number of neurons compared to humans, it still has a richness in its behavior. Finally, in the fruit fly we have powerful genetic toolkits that enable direct access to individual neurons within a circuit. We investigate sensorimotor circuits that drive escape behaviors to "looming" stimuli that mimic an object approaching on a direct collision course. Escape is one of the most explored animal behaviors since the behavioral principles are conserved across species due to its essential need for survival. In response to looming stimuli, animals can perform a variety of escape behaviors such as freezing, fleeing, jumping, and flight initiation. This flexibility has been hypothesized to emerge from parallel sensorimotor pathways that function to select and coordinate a behavioral response. Prior research has demonstrated that neural responses to looming stimuli are similar across species from vertebrates to invertebrates. However, the tuning properties of looming responsive neurons have not been well characterized, and few looming responsive neurons have been directly linked to behavioral outputs. Our data and recent data from other studies suggest at least four looming-evoked escape pathways may exist in the fly. Each pathway consists of a pair of descending neurons (DNs) that are thought to be a critical bottleneck in the flow of information from sensory systems in the brain to motor circuits in the ventral nerve cord (VNC, fly "spinal cord"). In this study we seek to understand how looming visual information is integrated across hemispheres in DNs to generate a relevant escape output. We determine key looming responsive DNs and investigate their directional tuning by developing a projection system for displaying looming stimuli while performing in-vivo whole-cell electrophysiology in behaving, tethered flies. We demonstrate an essential escape DN (DNp01, also called the giant fiber) has directionally invariant tuning to looming stimuli that may enable escapes regardless of the approach direction of an object. Finally, we investigate the mechanisms for bilateral looming integration in DNp01 by discovering a key commissural interneuron in the escape circuit. By investigating a highly conserved behavior, this study provides insight into the general mechanisms for sensorimotor integration across species.