Education:
1998-2002 B.Sc. in Engineering Mechanics, Department of Engineering Mechanics, Tsinghua University
2002-2004 M.Sc. in Engineering Mechanics, Department of Engineering Mechanics, Tsinghua University
2004-2010 Ph.D. in Applied mathematics, School of Engineering and Applied Science, Harvard University
Professional Positions:
2010-2015 Postdoctoral Fellow, HHMI-Janelia Research Campus, Virginia, USA
2015-2020 Assistant Professor, School of Medicine, Tsinghua University, Beijing, China
2020-2024 Associate Professor, School of Medicine, Tsinghua University, Beijing, China
2024-now Associate Professor, School of Basic Medical Sciences, Tsinghua University, Beijing, China
Research Areas:
The neural mechanisms of learning and memory. The human brain contains hundreds of different brain regions, which are connected by a complex network of neural fibers, forming a brain network that can flexibly process information in real-time based on different situations. Sensory information from the external world enters the brain and is temporarily stored in the form of working memory to guide the next steps of action. Working memory is the foundation for cognitive abilities such as learning, reasoning, decision-making, and consciousness.
This research in my lab primarily uses mice as the model system, combining optogenetics, multi-channel electrophysiology, two-photon imaging, and quantitative behavioral studies to investigate how neural networks across multiple brain regions promote the generation and maintenance of working memory information; how the dynamic changes in neural activity across these brain regions support the learning of working memory behaviors; and also develop new structural and functional imaging methods to facilitate the study of multi-regional neural dynamics.
Through the exploration of brain network functions, combined with novel technological approaches, the ultimate goal is to understand the underlying mechanisms of the working memory network, provide new insights for the treatment of working memory-related disorders, and inspire the development of innovative artificial intelligence computational models.
Research Achievements:
My lab has a long-term dedication to the research on the neural circuitry underlying working memory and the development of optical microscopy imaging technologies. For example, we have constructed one high-throughput approach to study the functional connectivity between different brain regions and used it to map the functional connectivity between the top cortical areas and the thalamus in awake mice, demonstrating the causal influences of various cortical regions on different thalamic nuclei. In mice performing working memory tasks, by combining optogenetic manipulation and multi-channel electrophysiology, we found that the output nuclei of the basal ganglia can specifically modulate the neural activity in the premotor cortex, leading to the generation of distinct neural activity patterns that encode the corresponding working memory. We also discovered that working memory can be maintained asymmetrically across the two brain hemispheres, and this asymmetry is determined by the interactions between the two hemispheres, where the dominant hemisphere governs the neural activity in the non-dominant hemisphere. This lateralized influence can explain the behavioral differences observed in mice across different tasks, individuals, and days. Additionally, we have developed multi-scale light-sheet microscopy and SMART spinning disk confocal imaging systems, enabling high-speed, high-resolution, and high-contrast whole-brain imaging of transparent mouse brains, which has allowed us to reconstruct the complete morphology of individual neurons.
The findings from this series of studies have been published as the first/corresponding author articles in prestigious international journals such as Nature, Nature Methods, Neuron (4 papers), Cell Reports, eLife, PNAS, and Molecular Psychiatry. I have also been invited to serve as an Associate Editor for the journal Science Advances. I have led multiple National Natural Science Foundation of China projects, as well as a major project from the Ministry of Science and Technology.
Honors and Awards:
Selected Publications:
1.Ocklenburg S and Guo ZV. Cross-hemispheric communication: Insights on lateralized brain functions. Neuron, 2024, 10.1016/j.neuron.2024.02.010
2.Zhang Y, Wang M, Zhu Q, Guo Y, Liu B, Li J, Yao X, Kong C, Zhang Y, Huang Y, Qi H, Wu J, Guo ZV & Dai H. Long-term mesoscale observation of native 3D intercellular dynamics across a mammalian organ by RUSH3D. Under review
3.Jaramillo J, and Guo ZV. Thalamocortical Contributions to Neural Dynamics and Behavior. Book Chap of the Cerebral Cortex and thalamus, Edited by Martin Usrey and S. Murray Sherman
4.Geng J, Tang Y, Yu Z, Gao Y, Li W, Lu Y, Wang B, Zhou H, Li P, Liu N, Wang P, Fan Y, Yang Y, Guo ZV and Liu X. Chronic Ca2+ imaging of cortical neurons with long-term expression of GCaMP-X. eLife, https://doi.org/10.7554/eLife.76691
5.Yin X, Wang W, Li J, and Guo ZV. Lateralization of short-term memory in the frontal cortex. Cell Reports, 2022. 40, 111190.
6.Lu J, Zhang Z, Yin X, Tang Y, Ji R, Chen H, Guang Y, Gong X, He Y, Zhou W, Wang H, Cheng K, Wang Y, Chen X, Xie P, and Guo ZV. An entorhinal-visual cortical circuit regulates depression-like behaviors. Molecular Psychiatry, 2022. 27, 3807–3820.
7.Wang Y, Yin X, Zhang Z, Li J, Zhao W and Guo ZV. A cortico-basal ganglia-thalamo-cortical channel underlying short-term memory. Neuron, 2021. 109, 3486-3499.
8.Zhang Z, Yao X, Yin X, Ding J, Huang T, Huo Y, Ji R, Peng H and Guo ZV. Multi-scale light-sheet fluorescence microscopy for fast whole brain imaging. Front neuroanat, 2021. 15: 732464
9.Chen H, Huang T, Yang Y, Yao X, Huo Y, Wang Y, Zhao W, Ji R, Yang H and Guo ZV. Sparse imaging and reconstruction tomography for high-speed high-resolution whole brain imaging. Cell reports methods, 2021. 1(6), 100089.
10.Lu J, Gong X, Yao X, Guang Y, Yang H, Ji R, He Y, Zhou W, Wang H, Wang W, Bai S, Guo H, Guo ZV* and Xie P*. Prolonged chronic social defeat stress promotes less resilience and higher uniformity in depression-like behaviors in adult male mice. Biochemical and Biophysical Research Communications. 2021. 553:107-13
11.Huo Y, Chen H and Guo ZV. Mapping functional connectivity from the dorsal cortex to the thalamus. Neuron, 2020. 107, 1080-1094.
12.Guo ZV, Inagaki HK, Daie K, Druckmann S, Gerfen CR and Svoboda K. Maintenance of persistent activity in a frontal thalamocortical loop. Nature. 2017. 545, 181-186.
13.Guo ZV, Hires SA, Li N, O'Connor DH, Komiyama T, Ophir E, Huber D, Bonardi C, Morandell K, Gutnisky D, Peron S, Xu N, Cox J, Svoboda K. Procedures for behavioral experiments in head-fixed mice. Plos one. 2014, 9(2): e88678.
14.Guo ZV, Li N, Huber D, Ophir E, Gutnisky D, Ting JT, Feng G and Svoboda K. Flow of cortical activity underlying a tactile decision in mice. Neuron. 2014, 81, 179-194.
15.Guo ZV, Hart AC and Ramanathan S. Optical interrogation of neural circuits in Caenorhabditis elegans. Nature Methods. 2009, 6, 891-896.
16.Guo ZV and Mahadevan L. Limbless undulatory propulsion on land. PNAS. 2008, 105(9), 3179-3184.
17.Z Guo and W Yang. MPM/MD handshaking method for multiscale simulation and its application to high energy cluster impacts. International Journal of Mechanical Sciences, 2006, 48(2), 145–159.
