Research interests:

Our goal is to understand principles underlying the development of motor circuits¹. We use gene expression to define classes of interneurons in the embryonic and adult nervous system. Once a gene is identified as a unique marker for a class of neurons, we target that locus using homologous recombination in the mouse embryonic stem cells. This approach allows us to generate transgenic mice in which a defined class of neurons expresses fluorescent markers for mapping its projections and identifying its synaptic partners. We also use transgenic methods to selectively ablate, silence or activate select neurons in the embryonic or adult mice. The goal of these studies is to determine the function of these neurons in motor control. We evaluate motor functions using a variety of electrophysiological and behavioral assays. Thus far we have studied the development² and functions^{3, 4} of a class of neurons called the V2a interneurons. These neurons are glutamatergic and are characterized by the expression of a homeodomain transcription factor Chx10.

1. Sharma, K. & Peng, C.Y. Spinal motor circuits: merging development and function. Neuron 29, 321-324. (2001).

2. Peng, C.Y., et al. Notch and MAML signaling drives Scl-dependent interneuron diversity in the spinal cord. Neuron 53, 813-827 (2007).

3. Crone, S.A., et al. Genetic ablation of V2a ipsilateral interneurons disrupts left-right locomotor coordination in mammalian spinal cord. Neuron 60, 70-83 (2008).

4. Crone, S.A., Zhong, G., Harris-Warrick, R. & Sharma, K. In mice lacking v2a interneurons, gait depends on speed of locomotion. J Neurosci 29, 7098-7109 (2009).

Recent Finding:

Most recent discovery is the identification of V2a interneurons as a key neural component for regulating gait at fast speeds of locomotion. We have found that wild type mice alternate left and right limbs at all speeds. When V2a interneurons are ablated in a transgenic line called Chx10::DTA, these mice use a hopping/galloping gait at fast speeds. This finding is best demonstrated in the following videos.

Wild type mouse

Chx10:DTA mouse