Scheme: Newton International Fellowships
Organisation: University of Cambridge
Dates: Mar 2009-Mar 2011
My research focuses on two key questions:
How do motor systems coordinate activity across many body segments?
How are developmental origins of neurons linked to their patterns of activity in motor systems?
One common feature of motor systems is that they can produce rhythmic activity in the absence of sensory feedback. Such central pattern generating (CPG) networks provide initial functional substrates in motor systems, which are then sculpted by sensory feedback and neuromodulation to ultimately produce movement. Despite decades of research in a variety of model organisms, we still have much to learn about how CPGs are assembled and how they generate rhythms. I am interested in understanding how CPGs coordinate activity across disparate body segments and how the developmental origins of cells within segmentally organized CPGs ultimately dictate their recruitment into motor patterns.
I’ve chosen to study these topics in larval Drosophila melanogaster. I work with the maggot motor system for three primary reasons: 1) it has evolved to precisely coordinate activity across many body segments, 2) it is genetically and electrophysiologically tractable at the level of single, identified neurons, and 3) the developmental origins of many cells within the network are well known.
As a postdoc, I developed an isolated nerve cord preparation that generates a range of fictive larval behaviors. I’m currently using this traditional type of CPG preparation along with calcium imaging and optogenetics to identify core rhythm generating circuits in the ventral nerve cord. I am also using patch clamp recordings to examine how the dynamics of intrinsic properties and identified synaptic connections ultimately generate and regulate segmentally coordinated rhythms. Importantly, in larvae we can also trace the developmental origins of identified cells back to individual neuroblasts. And in some cases, we know exactly when and how individual neurons are born. Long-term, I am keen to use this type of detailed developmental information as a context to understand the developmental origins of CPG circuit components within the larval locomotor system.
Overall, Drosophila as a model organism has a proven track record of uncovering conserved principles in neurobiology, so I am hopeful that by pursuing this program of research in flies, we will gain insight into how segmentally organized motor circuits generate movement in a wide variety of animals.