Assistant Professor, Baylor College of Medicine
B.S., Fudan University, Shanghai, 2001
Ph.D., Baylor College of Medicine, Houston, 2009
Postdoc, University of California, San Diego, 2009-14
Cortical circuit function and development in health and disease
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 our laboratory 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. 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.
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. Nature Structural and Molecular Biology 14:949-958.
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. Proceedings of the National Academy of Sciences USA 105:7875-7880.
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. Nature Structural and Molecular Biology 15:1160-1168.
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. Neuron 64:367-380.
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. Nature Structural and Molecular Biology 17:568-575.
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. Nature Neuroscience 16:1068-1076.
Xue M, AtallahBV, Scanziani M (2014) Equalizing excitation-inhibition ratios across visual cortical neurons. Nature (in press).
Mingshan Xue, Ph.D.
Department of Neuroscience
Baylor College of Medicine
1250 Moursund St. – NRI, Suite 1270.02
Houston, TX 77030
Tel: (832) 824-8109