Zengcai Guo
Email：zengcai.guo@gmail.com
Research Area:
Neural mechanisms of learning and memory.
The human brain contains hundreds of distinct regions interconnected by intricate neural fibers, forming networks that can flexibly and dynamically process information in real time under varying conditions. Sensory inputs from the external world enter the brain and are briefly stored as working memory to guide subsequent actions. Working memory underpins cognitive functions such as learning, reasoning, decision-making, and consciousness.
Our laboratory primarily uses mice as the model system and combines optogenetic manipulation, multi-channel electrophysiology, optical imaging, and quantitative behavioral tasks to investigate how multi-region neural networks generate and maintain working-memory representations; how neural dynamics across brain regions change in coordination to support the learning of working-memory behaviors; and to develop novel structural and functional imaging methods that advance the study of multi-region neural dynamics. By studying brain-network function and leveraging new technological approaches, we aim to elucidate the operational mechanisms of the working-memory network, provide new avenues for treating working-memory disorders, and inspire next-generation artificial intelligence computing models.
Selected Publications:
1.Long Z, Yu Y, He C, Xu L, Yan Y, Li Zhuoru, Guo ZV* & Mi D*. Intravital observations of neuronal and immune cell dynamics in the developing mammalian brain. Cell, Accepted.
2.Zhou S, Zhu Q, Eom M, Fang S, Subach OM, Ran C, Alvarado JS, Sunkavalli PS, Dong Y, Wang Y, Hu J, Zhang H, Wang Z, Sun X, Yang T, Mu Y*, Yoon Y*, Guo ZV*, Subach FV*, Piatkevich KD*. A sensitive soma-localized red fluorescent calcium indicator for in vivo imaging of neuronal populations at single-cell resolution. Plos Biology, 2025. 23, e3003048
3.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 Q*. Long-term mesoscale observation of native 3D intercellular dynamics across a mammalian organ by RUSH3D. Cell, 2024. 187, 6104-6122.
4.Ocklenburg S* and Guo ZV*. Cross-hemispheric communication: Insights on lateralized brain functions. Neuron, 2024. 112, 1222-1234.
5.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. pp. 367-380. Oxford University Press.
6.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, 2022, https://doi.org/10.7554/eLife.76691
7.Yin X, Wang W, Li J, and Guo ZV*. Lateralization of short-term memory in the frontal cortex. Cell Reports, 2022. 40, 111190.
8.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.
9.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.
10.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
11.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.
12.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
13.Huo Y, Chen H and Guo ZV*. Mapping functional connectivity from the dorsal cortex to the thalamus. Neuron, 2020. 107, 1080-1094.
14.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.
15.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.
16.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.
17.Guo ZV, Hart AC and Ramanathan S. Optical interrogation of neural circuits in Caenorhabditis elegans. Nature Methods. 2009, 6, 891-896.
18.Guo ZV and Mahadevan L. Limbless undulatory propulsion on land. PNAS. 2008, 105(9), 3179-3184.
19.Guo Z and Yang W. 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.
