Research
The circuits directly tasked with controlling limb movement are located in the spinal cord, where diverse collections of interneurons receive input from sensory and descending systems to control motor neuron firing. Despite their critical role in influencing movement, we know little about the functional organization of these interneurons and how they govern precise patterns of motor output. Our work takes advantage of the genetic accessibility of mice to dissect the identity and circuitry of spinal interneurons, with the goal of understanding how they interact with sensory input and descending systems in the brain to control movement. The lab focuses on three general research questions:
I. Cell-type diversity in the nervous system
Understanding the functional organization of the nervous system relies in part on defining the diversity and identity of neuronal cell types that form the building blocks of neural circuits. Our prior work has focused on the cardinal class of spinal V1 interneurons, which are the largest inhibitory population in the ventral spinal cord, and are known to play key roles in coordinating flexion/extension movement and regulating locomotor speed. We found that the V1 class contains dozens of candidate cell types that differ in their molecular identity, position, and physiology. In ongoing work, we are employing single-cell genomic and computational approaches to further define the identity and gene regulatory networks that specify these different interneuron cell types.
II. Connectivity of spinal motor circuits
We are interested in the circuit organization and synaptic connectivity of spinal interneurons. By using viral transsynaptic and other tracing methods, in combination with whole-brain imaging, we aim to define the extent to which V1 interneuron subsets are recruited by distinct descending systems in the brain and project to motor pools controlling biomechanically distinct muscles.
III. Function of spinal interneurons in motor control
The ventral interneurons we study are known to provide direct synaptic input to motor neurons. By virtue of their proximity to motor output, these interneurons represent an excellent system to study how manipulation of neural activity leads to changes in behavior. Using the genetic accessibility of mice to target specific spinal interneuron subsets, in combination with electromyography and high-speed imaging and kinematic analysis, we can study how ablation or activation of neuronal subsets perturbs fundamental aspects of limb movement, such as flexion/extension.
