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
Each brain region contains distinct neuronal cell types with characteristic morphological, electrophysiological and transcriptomic properties, and these different types of neurons are wired in a specific manner to form a functional microcircuit. 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 related questions regarding cortical microcircuit: (1) how different cortical cell types connect each other to form a normal, functional circuit and (2) how stereotypical wiring principles among distinct cell types are impacted by distinct neuropsychiatric conditions. 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 individual neurons in cortical microcircuit at each and every level, including their electrophysiological properties, morphology, transcriptome and connections, in order to decipher the comprehensive blueprint of the cortical microcircuit. 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 reverse-engineer cortical microcircuit by revealing its essential building blocks and the specific functional role each constituent performs.
Once we decipher the canonical circuit blueprint in normal heathy brain, we further use this knowledge as a template to reveal aberrant connections between specific cell types (connectopathies) underlying distinct neuropsychiatric disorders, including epilepsy, autism-spectrum disorders and schizophrenia. Extensive research has done to probe these disorders at genetic/molecular, macro-scale, and behavior level. However, at the meso-scale level, how each neuropsychiatric condition impacts the circuit blueprint remains largely unknown. In addition, within each disorder, there are distinct etiologies that share a similar symptomatology and EEG signature, raising the possibility that different etiologies induce the same circuit wiring deficits that result in the same phenotypes. To explore if there is a stereotypical circuit wiring deficit underlying absence epilepsy despite disparate molecular lesions, we use two mouse models of absence epilepsy, stargazer and tottering, which harbor distinct monogenic mutations but have the same epileptic phenotype. We perform an unbiased, large-scale microcircuit analysis on both models at the level of cell types and connections to reveal detailed circuit blueprint change as a function of genotype. 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 deficits for a specific type of neuropsychiatric diseases paves the way for more universal, 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: