Research

The Agrawal lab seeks to understand how sensorimotor circuits have evolved to encode limb movement and coordinate behavior, thus enabling animals to operate in an ever-changing environment. 

How does proprioceptive feedback rapidly coordinate ethologically important behaviors?

Performing a successful landing is arguably the most important step of flight. When landing, flying animals must quickly and precisely coordinate multiple limbs to transition to a stable standing posture, often on surfaces varying in stability, texture, and orientation. Proprioceptive sensory neurons on the legs signal surface contact and the distribution of body load across the legs. These neurons are therefore likely key to coordinating successful landings, but have yet to be studied.

We have developed a novel behavioral assay using the fruit fly to determine how proprioceptive feedback coordinates limb movements during landing. We induce landing in tethered, flying flies by elevating a platform to contact their legs, mimicking the contact that occurs during landing. We then track the 3D kinematics of leg joints, wings, and body of flies as they respond to this contact. We are using this system to understand how mechanical perturbation of the legs influences landing, the different sub-behaviors that comprise landing, and the proprioceptive sensory neurons that mediate landing.

How does the CNS integrate information across diversely tuned proprioceptive sensory neurons?

Animals possess diverse limb proprioceptors that encode different body kinematics. Although proprioceptive feedback is crucial for accurate motor control, little is known about how downstream circuits in the CNS extract relevant features from such complex patterns of activity across diverse proprioceptor populations. This gap in our knowledge is because proprioceptive submodalities such as load sensing and movement sensing have primarily been studied separately. 

We are currently developing tools to study load-sensing in the fruit fly. Then, together with previously developed tools, this new model will enable us to define the circuit-level mechanisms that are key to multimodal integration of load and movement sensing and proprioceptive control of movement. Understanding how the CNS overcomes the challenge of efficient multimodal integration will reveal how our bodies use proprioceptive information to coordinate everyday motor tasks, a critical step towards the eventual development of therapies ameliorating proprioceptive dysfunction.

How have proprioceptive circuits co-evolved with changes in limb shape, body size, behavior, or environment?

While comparative work suggests that proprioceptive systems are functionally conserved across species, animals vary in size, shape, muscle types, gaits, and environments. We know little about how such variations impact the function and organization of proprioceptive circuits. 

Insects are an exceedingly diverse group of animals, with performance demands that are reflected in their limb morphologies and life histories. This diversity presents an opportunity to reveal principles of mechanosensory feedback and generalize our understanding of proprioceptive encoding beyond examples in a few model systems. Towards this end, we are performing a comparative morphological study of campaniform sensilla (CS) on the legs of different insect species. We are quantifying anatomical parameters such as sensor density, shape, size, and position and then correlating them with limb shape, body size, walking gait, wingbeat frequency, and evolutionary history to uncover the degree to which evolution acts on factors such as location, shape, and density to enable CS to encode relevant stimuli. This correlation will result in several hypotheses as to how sensor placement varies with limb shape which we will then test via biomechanical modelling and robotic simulations. 

Can we target proprioception as a means to control the deadly disease vector, Aedes aegypti?

We have developed tools to examine the encoding of FeCO neurons in the mosquito Aedes aegypti. Mosquitoes and fruit flies are both dipteran insects, but they diverged approximately 260 millions years ago. Both animals possess an FeCO that encodes movement and position of the femur-tibia joints of the legs, but they vary in leg length, body size, and their walking kinematics. We seek to determine how evolutionary forces have shaped the structure and function of this mechanosensory organ. We hypothesize that the structure and encoding of the FeCO will vary in mosquitoes reflecting the different behavioral demands of mosquito leg motor control. Finally, several pesticides exist that target mechanosensory neurons like chordotonal organ neurons. We will test whether we can use them to effectively perturb mosquito behavior, focusing on epidemiologically-relevant behaviors that utilize the FeCO.