Xiaolong Jiang, Ph.D.
Assistant Professor, Department of Neuroscience, Baylor College of Medicine and Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital
Dissecting cortical microcircuits in health and disease; connectopathies in epilepsy and autism-spectrum disorders
Each brain region contains distinct neuronal cell types with characteristic morphological, electrophysiological and neurochemical properties, and these different kinds of neurons are wired in a stereotypical manner into functional circuits. A mechanistic understanding of the workings of the normal and pathological brain requires identifying all of the constituent cell types, mapping their interconnections and determining their functions.
The Jiang Laboratory focuses on two fundamental questions regarding cortical microcircuits: (1) how many cell types exist in a cortical microcircuit and (2) how do they connect to each other to form a functional circuit? To this end, we developed and employ a multi-disciplinary approach that includes multi-cell patching (up to 12 simultaneous patching) in brain slices, detailed morphological recovery, single-cell RNA sequencing of patched cells (patch-seq), optogenetic techniques, machine learning, and sophisticated mouse genetic models. Using this integrated approach, we perform large-scale, unbiased profiling of the neurons in the adult cortical microcircuit at each and every level, including their electrophysiological properties, morphology, transcriptome and connections. We also use in vivo whole cell recordings, two-photon Ca2+ imaging and behavioral assays to explore cell-type specific roles in the information processing of intact brains. Our ultimate goal is to build a complete picture of the wiring diagram of cortical microcircuits by revealing their essential building blocks and organizational principles.
In parallel, we employ the same approach on animal models of neuropsychiatric disorders to examine if aberrant connections between specific cell types (connectopathies) underlie a wide variety of neuropsychiatric disorders, including epilepsy, autism-spectrum disorders and schizophrenia. Extensive research in the past has identified a wide variety of etiologies for neuropsychiatric disorders. However, at the meso-scale level, how each etiology changes the wiring diagram of cortical microcircuits remains largely unknown. In addition, within each disorder, there are distinct etiologies that generally share a common symptomatology and EEG signature, raising the possibility that different etiologies induce the same wiring deficits in the brain that mediate behavioral symptoms. Therefore, it is important to examine if a stereotypical wiring deficit underlies these brain disorders. To explore shared circuit wiring deficits between different epilepsy models, we are currently studying the microcircuits of “stargazer” and “tottering” mice, two mouse models of absence epilepsy that result from two distinct single-gene mutations but have the same symptoms. Similarly, we are using different mouse models of ASD, including (Angelman syndrome and Rett syndrome) to examine if there are stereotypical wiring abnormalities across different ASDs. Identifying the stereotypical circuit dysfunction for a specific type of neuropsychiatric diseases paves the way for common circuit-based cell-type specific interventions for these diseases.
1. Xiaolong Jiang, Guangfu Wang, Jisoo Lee, Ruth Stornetta, Julius Zhu. The organization of two new interneuronal circuits. Nature Neuroscience. 2013 Feb;16(2):210-8.
2. Lee J*, Wang G*, Jiang X*, Johnson SM, Hoang ET, Lanté F, Stornetta RL, Beenhakker MP, Shen Y, Julius Zhu J. Canonical Organization of Layer 1 Neuron-Led Cortical Inhibitory and Disinhibitory Interneuronal Circuits. Cereb Cortex. 2014 Feb 18. *co-first authors
3. Wang G, Wyskiel DR, Yang W, Wang Y, Milbern LC, Lalanne T, Jiang X, Shen Y, Sun QQ, Zhu JJ. An optogenetics- and imaging-assisted simultaneous multiple patch-clamp recording system for decoding complex neural circuits. Nat Protoc. 2015 Mar; 10(3):397-412.
4. Jiang X*, Shen S, Cadwell CR, Berens P, Sinz FH, Ecker A, Patel S, Tolias AT*. The principles of connectivity among morphologically defined neuronal types in adult neocortex. Science. 2015 Nov 27; 350(6264):aac9462. *co-corresponding authors
5. Cadwell CR, Palasantza A, Jiang X, Berens B, Deng Q, Yilmaz M, Reimer J, Bethge M, Tolias KF, Sandberg R and Tolias AS. High-throughput morphological, electrophysiological and transcriptomic profiling of single neurons. Nature Biotechnology . 2015 Dec 21.
6. Jiang X, Chen A, Li H. Histaminergic Modulation of Excitatory Synaptic Transmission in the Rat Basolateral Amygdala. Neuroscience. 2005; 131(3): 691-703.
7. Xiaolong Jiang, Guoqiang Xing, Chunhui Yang, Ajay Verma, Lei Zhang and He Li. Stress Impairs 5-HT2A Receptor Mediated Serotonergic Facilitation of GABA Release in Juvenile Rat Basolateral Amygdala. Neuropsychopharmacology.2009 Jan; 34(2):410-23. Epub 2008 Jun 4.
8. Xiaolong Jiang, Zhang-Jin Zhang, Steven Zhang, Robert Ursano and He Li. 5-HT2A Receptor Antagonism by MDL 11,939 during Inescapable Stress Blocks Subsequent Exaggeration of Acoustic Startle Response and Reduced Body Weight in Rats. Journal of Psychopharmacology. 2009 Nov 4. [Epub ahead of print].
Complete List of Publications: