Neuroscience at The University of Chicago

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 functions3, 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).

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Chian-Yu Peng, Hiroshi Yajima, Caroline Erter Burns, Leonard I. Zon, Sangram S. Sisodia, Samuel L. Pfaff, Kamal Sharma. (2007) Notch and MAML regulate Scl-dependent Interneuron Cell Fate in the Spinal Cord. Neuron. 53, 813-827.

Highlighted in Faculty of 1000

Wang, L., Sharma, K., Deng, H.X., Siddique, T., Grisotti, G., Liu, E., and Roos, R.P. (2008). Restricted expression of mutant SOD1 in spinal motor neurons and interneurons induces motor neuron pathology. Neurobiol Dis 29, 400-408

Crone, S.A., Quinlan, K.A., Zagoraiou, L., Droho, S., Restrepo, C.E., Lundfald, L., Endo, T., Setlak, J., Jessell, T.M., Kiehn, O., and Sharma, K. (2008). Genetic ablation of V2a ipsilateral interneurons disrupts left-right locomotor coordination in mammalian spinal cord. Neuron 60, 70-83

Highlighted in Faculty of 1000

Wang, L., Sharma, K., Grisotti, G., and Roos, R.P. (2009). The effect of mutant SOD1 dismutase activity on non-cell autonomous degeneration in familial amyotrophic lateral sclerosis. Neurobiol Dis 35(2):234-40

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