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
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.