Faculty & Research

Mingshan Xue, Ph.D.

Caroline DeLuca scholar and Assistant Professor, Department of Neuroscience, Baylor College of Medicine and the Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital

Cortical circuit, synaptic excitation and inhibition, epilepsy and autism   

 

The cerebral cortex of the mammalian brain uses seemingly slow neural circuits to perform incredible functions that cannot be achieved by much faster man-made devices. Clearly, the cortex has evolved distinct circuit elements to implement such efficient computations, ultimately giving arise to sensation, thoughts, and actions. The research goal of the Xue lab is to understand how different elements of cortical circuits interact with each other via synaptic connections to perform cortical functions, and how dysfunction or abnormal development of neural circuits contributes to the pathogeneses of neurological disorders.   

Distinct types of excitatory and inhibitory neurons form the basic elements of cortical circuits. They generate synaptic excitation and inhibition, two major forces that control neuronal activity in the cerebral cortex. Cortical function critically depends on the interplay between synaptic excitation and inhibition. Their ratio (E/I ratio) is fundamental to many functional properties of cortical neurons, such as feature selectivity, spike timing, gain, and dynamic range. Failure to establish or maintain a proper E/I ratio is being increasingly recognized as a key etiology of many neurological disorders such as autism spectrum disorder and epilepsy. In the Xue lab, we study the spatiotemporal distribution of E/I ratio in distinct types of cortical neurons in order to understand how the interaction between excitation and inhibition results in coordinated cortical activity. Furthermore, we aim to identify the mechanisms by which genetic programs and activity-dependent processes establish and maintain the proper E/I ratios for different cell types. Finally, we investigate how abnormal E/I ratio perturbs cortical functions in the animal models of autism spectrum disorder and childhood epilepsy. A wide variety of approaches are employed in our laboratory including molecular manipulations (e.g. transgenic mouse, recombinant virus), functional manipulations (e.g. opto-genetics, chemical-genetics), structural and functional analyses (e.g. in vitro and in vivo electrophysiology, two-photon imaging), gene expression profiling, and behavioral assays. Our goal is to elucidate the synaptic mechanisms of elementary circuit functions with the hope to develop strategies to re-instate the proper balance between excitation and inhibition in neurological disorders for therapeutic interventions.

Publications

1) Xue M, AtallahBV, Scanziani M (2014) Equalizing excitation-inhibition ratios across visual cortical neurons. Nature 2014 Jun 22. doi: 10.1038/nature13321. [Epub ahead of print]

2)  Pfeffer CK, Xue M, He M, Huang ZJ, Scanziani M (2013) Inhibition of inhibition in visual cortex: the logic of connections between molecularly distinct interneurons. Nat Neurosci16:1068-1076.

3)  Xue M, Craig TK, Xu J, Chao HT, Rizo J, Rosenmund C (2010) Binding of the complexin N terminus to the SNARE complex potentiates synaptic-vesicle fusogenicity. Nat Struct Mol Biol 17:568-575.

4) Xue M, Lin YQ, Pan H, Reim K, Deng H, Bellen HJ, Rosenmund C (2009) Tilting the balance between facilitatory and inhibitory functions of mammalian and Drosophila Complexins orchestrates synaptic vesicle exocytosis. Neuron64:367-380.  

5)  Xue M, Ma C, Craig TK, Rosenmund C, Rizo J (2008) The Janus-faced nature of the C2B domain is fundamental for Synaptotagmin-1 function. Nat Struct Mol Biol 15:1160-1168. 

6)  Xue M, Stradomska A, Chen H, Brose N, Zhang W, Rosenmund C, Reim K (2008) Complexins facilitate neurotransmitter release at excitatory and inhibitory synapses in mammalian central nervous system. Proc Natl Acad Sci USA105:7875-7880.

 7) Xue M, Reim K, Chen X, Chao HT, Deng H, Rizo J, Brose N, Rosenmund C (2007) Distinct domains of complexin I differentially regulate neurotransmitter release. Nat Struct Mol Biol 14:949-958.

Contact Information

Mingshan Xue, Ph.D.

Email:
mxue@bcm.edu

Phone:
832-824-8109
832-825-1249 (Fax)

Address:
Department of Neuroscience,
Baylor College of Medicine,
Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital 
1250 Moursund St.  NRI, Suite 1270.02 
Houston, TX 77030

To learn more:
Contact: nri_info@texaschildrens.org