| Understanding the neural circuits and genes that underlie behavior is a fundamental question in the field of neuroscience. While behaviors diverge across species, recent structural analysis of neural anatomy suggests that many patterns of neural connectivity are conserved across species. These neural motifs can be thought of as building blocks that may be increased or reconfigured to generate nervous system complexity. It can be difficult to define and characterize properties of neural circuits in complex systems, such as the human brain, which possesses an estimated 100 billion neurons and 3 trillion synapses. In contrast, with only 302 neurons and 7,000 synapses, the genetic model, Caenorhabditis elegans, has become an attractive system to dissect how neural circuits and genes generate behavior. Caenorhabditis elegans exhibits a number of complex behaviors, all of which involve basic locomotion. During locomotion, worms initiate backward movement to change direction spontaneously or in response to sensory cues; however, the underlying neural circuits are not well defined. We applied a multidisciplinary approach to map neural circuits in freely behaving worms by integrating functional imaging, optogenetic interrogation, genetic manipulation, laser ablation, and electrophysiology. Using this approach, we discovered that the long standing model for backward movement in Caenorhabditis elegans required substantial revision. Previously, it was thought that a set of command interneurons acting as a stimulatory circuit were required to drive backward movement. We discovered that although important for execution and coordination, backward movement persisted in the absence of the command interneurons. Importantly, we identified a new disinhibitory circuit that acts in parallel to the stimulatory circuit to promote initiation of backward movement and that circuitry dynamics is differentially regulated by sensory cues. Both circuits require glutamatergic transmission but depend on distinct glutamate receptors. This dual mode of motor initiation control is found in mammals, suggesting that distantly related organisms with anatomically distinct nervous systems may adopt similar strategies for motor control. Additionally, our studies illustrate how a multidisciplinary approach facilitates dissection of circuit and synaptic mechanisms underlying behavior in a genetic model organism. |
