I am an enthusiastic, determined, skillful young scholar that has been working in neuroscience field for over 10 years. My expertise includes in vivo optogenetics, chemogenetics, electrophysiology, rodent behavior assays, viral-based circuit mapping, high-resolution microscopy imaging, molecular and cellular biology, as well as adapting and integrating cutting-edge techniques such as fiber photometry and fMRI to investigate neural circuit. My career goal is to transition to an independent faculty position.
My primary research interest is to understand the essential cognitive functions in the brain.
During my early graduate training, I pioneered combining electrophysiology and optogenetics in Li lab, and applied these techniques to various neuropsychiatric diseased models. After I joined Song lab, I focused my study to adult hippocampal neurogenesis. Adult neurogenesis, the most striking demonstration of neural plasticity in adult brain, associating neural development with experience, epitomizes my greatest interest and passion. During my graduate training in Song lab, I used optogenetics, chemogenetics, along with pseudorabies tracing to dissect and manipulate septohippocampal GABAergic projection, and found its capability of bidirectionally regulating the quiescence of neural stem cells in dentate gyrus (DG) through DG-parvalbumin interneurons. This is the first study showing the circuit mechanism of how distal circuit interacts with neurogenic niche through hippocampal local interneurons. I had the honor to present my findings at SFN nanosymposium in 2016, and the paper was published in Cell Stem Cell as cover featured article in 2017 (shown above).
My short-term research goal is to study the interaction between adult neurogenesis and brain function both at circuit and behavior level, especially how adult-born neurons integrate to the circuit and contribute to cognition. Furthermore, I want to investigate comprehensive mechanisms of multi-layer network that is associated with adult neurogenesis, and understand the general principles of cognitive functions. My long-term research goal is to translate the knowledge to relevant neuropsychiatric disorders and provide circuit strategies to developing novel clinical diagnosis and therapies to benefit patients.
My Contributions to Science
- Cognitive dysfunction is one of the major deficits in many neurological and psychiatric diseases. The mechanisms and pathologies of these diseases are largely uncovered. To address these questions, I started my early graduate school training in Li lab at SJTU and focused my study on neuropsychiatric diseased animal models. One of my projects is to characterize the physiological function of a psychiatric susceptible gene disrupted-in-schizophrenia-1 (DISC1) in an inducible DISC1-N model, which can overexpress DISC1 N-fragment to competitively inhibit normal DISC1 function. I applied behavior assays along with in vivo electrophysiology recordings in mPFC to investigate this model and found that female DISC1-N mice showed deficits in social interaction and forced swimming and the neural firing property during these behaviors are largely altered. Using the same techniques, I studied another diseased model NF1+/- (neurofibromatosis type 1) heterozygous null mice, which has been reported for memory deficits. Our study showed altered MAPK pathway activity in NF1+/- mice could be associated with disrupted hippocampal theta oscillation, which linked cellular activity and global neuronal functions. These in vivo studies of diseased animal models provide us insights and potential mechanisms of various pathological conditions, which might be adapted for clinical diagnosis and treatment.
a) Chen L, Serdyuk T, Yang B, Wang S, Chen S, Chu X, Zhang X, Song J, Bao H, Zhou C, Wang X, Dong S, Song L, Chen F, He G, He L, Zhou Y, Li W. Abnormal circadian oscillation of hippocampal MAPK activity and power spectrums in NF1 mutant mice. Mol Brain. 2017 Jul 3;10(1):29.
b) Song W, Zhang K, Sun J, Ma L, Jesse FF, Teng X, Zhou Y, Bao H, Chen S, Wang S, Yang B, Chu X, Ding W, Du Y, Cheng Z, Wu B, Chen S, He G, He L, Chen X, Li W. A simple spatial working memory and attention test on paired symbols shows developmental deficits in schizophrenia patients. Neural Plasticity. 2013;2013:130642.
c) Bao H, Zhou Y, Guo L, Li W. Chronic recording techniques in DISC1-N mice. International Symposium on Molecular Cognition and Translation Research of Neuropsychiatric Disorders 2012 (Poster presentation)
- Adult hippocampal neurogenesis not only demonstrates the constantly ongoing neural plasticity, but also plays a critical role in learning and memory and in emotional regulation. However, how this dynamic process is regulated by neural circuit still remains uncovered. In my second phase of graduate school, I joined Song lab at UNC as a research assistant for collaboration and started to pursue this challenging question. My expertise including optogenetics, chemogenetics, pseudorabies-based circuitry mapping allowed me to dissect and specifically manipulate the neural circuits that interact with the neurogenic niche. We found that the distal septohippocampal GABAergic projections send predominant collaterals targeting DG-PV neurons, which act as intermediators to further regulate quiescence activity of neural stem cells. This study identified how distal inputs and local circuit jointly regulate hippocampal adult neurogenesis. Another related study I involved discovered the balance between DG hilar glutamatergic mossy cells and GABAergic interneurons can regulate adult neurogenesis as well. In addition, we developed AAV4-based viral tools to specifically target and manipulate neural stem cells. Overall, our works not only provide mechanisms of how adult neurogenesis is regulated in an activity-dependent manner, but also provide potential circuit components to serve as therapeutic targets, which might be largely beneficial to manipulate adult neurogenesis indirectly.
a) Bao H#, Asrican B#, Li W#, Gu B, Wen Z, Lim SA, Haniff I, Ramakrishnan C, Deisseroth K, Philpot B, Song J. Long-Range GABAergic Inputs Regulate Neural Stem Cell Quiescence and Control Adult Hippocampal Neurogenesis. Cell Stem Cell. 2017 Nov 2;21(5):604-617.e5. doi: 10.1016/j.stem.2017.10.003. (# Co-first authors, Cover featured article, Recommended by F1000, Best of 2017 Cell Stem Cell)
b) Yeh CY, Asrican B, Moss J, Quintanilla LJ, He T, Mao X, Cassé F, Gebara E, Bao H, Lu W, Toni N, Song J. Mossy Cells Control Adult Neural Stem Cell Quiescence and Maintenance through a Dynamic Balance between Direct and Indirect Pathways. 2018 Aug 8;99(3):493-510.e4. (Featured article, issue highlights)
c) Crowther AJ, Lim SA, Asrican B, Albright BH, Wooten J, Yeh CY, Bao H, Cerri DH, Hu J, Shih Y, Asokan A, Song J. An Adeno-Associated Virus-Based Toolkit for Preferential Targeting and Manipulating Quiescent Neural Stem Cells in the Adult Hippocampus. Stem Cell Reports. 2018 Mar 13;10(3):1146-1159. (Cover article)
d) Bao H, Song J. Treating Brain Disorders by Targeting Adult Neural Stem Cells. Trends Mol Med. 2018 Nov 14. pii: S1471-4914(18)30187-4. doi: 10.1016/j.molmed.2018.10.001 (Cover featured article, Invited review)
- Mounting evidence suggests that cognitive deficits of neuropsychiatric disorders may arise in part from a small number of dysregulated adult-born neurons in the DG. However, the exact mechanisms of how dysregulated adult-born neurons contribute to brain-wide maladaptation in neural circuit function and cognitive deficits remain largely unknown. In my current position as postdoctoral associate at UNC, I adapted my primary interest by combining cognition and adult neurogenesis. I took up the challenge to address how aberrant adult-born neurons intergrade into the circuit, transmit information, coordinate with other brain regions, and eventually alter cognitive performance. To study that, we used a well-characterized adult neurogenesis deficient model, which has downregulation of DISC1 in DG adult-born neurons. We found that only ~500 DISC1 deficient adult-born neurons are sufficient to significantly decrease the functional correlation between DG and distal insular cortex (IC), and alter IC neural activity in free moving mice. Importantly, our rabies-based retrograde tracing data suggested that DG and IC do not have direct anatomical connections, and the distal thalamic region might serve as an intermediator in this DG-IC network. These findings provide us essential circuit insights of how dysregulated adult hippocampal neurogenesis in DG disrupts brain-wide functional network, and may lead to a better understanding of neuropsychiatric disorders. Our manuscript is in preparation and will be submitted shortly.
a) Bao H, Hu Z, Lee S, Kolagani R, Chao T, Wickersham I, Shin Y, Song J. Dysregulation of Hippocampal Adult-Born Neurons Disrupts Brain-Wide Functional Network. 2019. (in manuscript)
Oral Presentation
- 2019 Society for Neuroscience, Chicago. (selected nanosymposium speaker)
- 2019 Society for Neuroscience, Trainee Professional Development Awards Poster presentation, Chicago. (invited awardee presentation)
- 2019 Pharmacology Research Retreat, UNC Chapel Hill, NC (selected speaker, best oral presentation)
- 2017 Shenzhen Institutes of Advanced Technology, Shenzhen, China. (invited speaker)
- 2016 Society for Neuroscience, San Diego. (selected nanosymposium speaker)
- 2012 International Symposium on Molecular Cognition and Translation Research of Neuropsychiatric Disorders, Shanghai, China (poster presentation)
Hechen's Scientific Studio 