Kamal Sharma

Neural circuits within the spinal cord generate commands for motor tasks such as locomotion. We are using a combination of genetic tools and physiological recordings to investigate:

(1) Which neuronal subtypes in the spinal cord make synaptic connections with the motor neurons?

(2) What is the precise function of these neuronal subtypes in the generation of appropriate motor output during locomotion?

The main driving force behind our experimental approach is the availability of a number of genetic markers and regulatory sequences that are specific to neuronal subtypes within the spinal cord. In combination with a novel approach for reversibly silencing neurons by transgene expression, we hope to generate information about the function of many different spinal interneurons in the generation of motor patterns. These data will provide a map of the synaptic information flow, much as blocking activity of specific enzymes was used to understand complex, often interwoven, metabolic pathways.

Research techniques:

(1) Analysis of gene expression
(2) Generation of transgenic mice and in-ovo electroporation for gene misexpression
(3) Morphological analysis of neuronal connections
(4) Physiological evaluation of the motor function

Neural circuits within the spinal cord generate commands for motor tasks such as locomotion. We are using a combination of genetic tools and physiological recordings to investigate:

(1) Which neuronal subtypes in the spinal cord make synaptic connections with the motor neurons?

(2) What is the precise function of these neuronal subtypes in the generation of appropriate motor output during locomotion?

The main driving force behind our experimental approach is the availability of a number of genetic markers and regulatory sequences that are specific to neuronal subtypes within the spinal cord. In combination with a novel approach for reversibly silencing neurons by transgene expression, we hope to generate information about the function of many different spinal interneurons in the generation of motor patterns. These data will provide a map of the synaptic information flow, much as blocking activity of specific enzymes was used to understand complex, often interwoven, metabolic pathways.

Research techniques:

(1) Analysis of gene expression
(2) Generation of transgenic mice and in-ovo electroporation for gene misexpression
(3) Morphological analysis of neuronal connections
(4) Physiological evaluation of the motor function

In mice lacking V2a interneurons, gait depends on speed of locomotion. Crone SA, Zhong G, Harris-Warrick R, Sharma K. J Neurosci. 2009 May 27;29(21):7098-109.  

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

Genetic ablation of V2a ipsilateral interneurons disrupts left-right locomotor coordination in mammalian spinal cord. Crone SA, Quinlan KA, Zagoraiou L, Droho S, Restrepo CE, Lundfald L, Endo T, Setlak J, Jessell TM, Kiehn O, Sharma K. Neuron. 2008 Oct 9;60(1):70-83.  

In mice lacking V2a interneurons, gait depends on speed of locomotion. Crone SA, Zhong G, Harris-Warrick R, Sharma K. J Neurosci. 2009 May 27;29(21):7098-109.  

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

Genetic ablation of V2a ipsilateral interneurons disrupts left-right locomotor coordination in mammalian spinal cord. Crone SA, Quinlan KA, Zagoraiou L, Droho S, Restrepo CE, Lundfald L, Endo T, Setlak J, Jessell TM, Kiehn O, Sharma K. Neuron. 2008 Oct 9;60(1):70-83.