Functional and Molecular Imaging; Neural Development and Plasticity; Neurological Disorders; and Synapses and Circuits
Dr. Gu received her B.S. and M.S. degrees from Tsinghua University, and Ph.D. degree from Johns Hopkins University. Her Ph.D. work in Dr. Richard Huganir’s laboratory was focused on the molecular and cellular regulation of neurotransmitter receptor trafficking.
Dr. Gu was trained as a postdoctoral fellow in the laboratory of Dr. David Tank at Princeton University, where she investigated the functional mechanism of the medial entorhinal cortex during spatial navigation by combining in vivo imaging with virtual reality behavioral paradigms. Dr. Gu joined NINDS as an investigator in 2019. Her research aims to understand the neural basis of spatial navigation and memory.
Research Interests:
The Spatial Navigation and Memory Unit is a systems neuroscience lab that primarily uses in vivo optical approaches to investigate the neural basis of spatial cognition in health and disease.
Spatial navigation is one of the most fundamental functions of the brain. Our research is focused on the neural basis of spatial navigation and memory, with the ultimate goal to uncover the fundamental principle of spatial cognition and the cause of related neurological disorders.
We are primarily interested in the medial entorhinal cortex (MEC), which plays a key role in spatial representation and episodic memory. The MEC is a part of medial temporal lobe and serves as the main gateway between the hippocampal formation and the neocortex. Many functional cell types, including grid cells, head-direction cells, border cells, speed cells, and object vector cells, have been discovered in the MEC and their activity patterns potentially represent spatial and self-motion information during navigation. Dysfunction of the MEC is closely associated with Alzheimer’s Disease (AD), the most common form of dementia. AD patients generally exhibit severe loss of episodic memory and have difficulty in spatial navigation.
Projects in the laboratory are centered around the following questions:
- How is spatial information represented and computed in the MEC circuit?
- Whether and how is spatial memory encoded in the MEC?
- How does the MEC interact with other brain areas to perform its function?
- How is the physiological function of the MEC disrupted in Alzheimer’s Disease?
We mostly use mice as model organisms and our experiments integrate optical, behavioral, computational, and molecular approaches. We access the MEC at cellular and sub-cellular resolution using two-photon imaging approach when mice navigate in virtual reality environments (see figures and videos below). This experimental setting provides a great opportunity to measure and manipulate neural dynamics while controlling spatial information during the navigation. In addition, we have a long-standing interest in developing new experimental paradigms to investigate circuit and molecular mechanisms underlying the MEC neural dynamics, as well as probing the function of the MEC in broader cognitive aspects.
Lab Members
- Dr. Yan Ma, Lab Manager
- Dr. Taylor Malone, Postdoctoral Fellow
- Dr. Lujia Chen, Postdoctoral Fellow
- Dr. Ellane Barcelon, Postdoctoral Fellow
- Dr. Kai Zhang, Postdoctoral Fellow
- Kyle Cekada, Postbaccalaureate IRTA
- Farid Shahid, Postbaccalaureate IRTA
- Duc Nguyen, Volunteer
Lab Alumni
- Daniel Yusufi (2024 June to August, summer student)
- Kevin Zhang (2024 June to August, summer student)
- Garret Wang (Postbac)
- Jean Tyan (Postbac)
- Nai-Wen Tien (Postdoc): Postdoctoral Scientist, Washington University School of Medicine in St. Louis
- Tiffany Rodriguez (2023 June to August, summer student)
- Lian Cui (Lab manager)
- Shangru Lyu (Postdoc): Scientist, Moderna
Collaborators
- Ila Fiete, McGovern Institute, Massachusetts Institute of Technology
- David A. Kupferschmidt, Integrative Neuroscience Section, National Institute of Mental Health, National Institutes of Health
- Shen-Ju Chou, Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan, Republic of China
Join Our Lab
We are constantly recruiting talented, motivated and friendly postdoctoral candidates with experience in in vivo imaging/recording, animal behavior, data analysis, and computational modeling. We also welcome applications from graduate and undergraduate students with background in Neuroscience and related areas. Please contact Dr. Gu if you are interested in joining us!
Building 35 Room 1C-1004
Convent Drive
Bethesda MD 20892
Office: 301-594-1501
Email: Yi Gu, Ph.D.
Selected Publications
The entorhinal spatial map integrates visual identity information of landmarks (2025). Biorxiv
Garret Wang, Farid Shahid, Taylor Malone, Jean Tyan, Kyle Cekada, Yi Gu#
The medial entorhinal cortex encodes multisensory spatial information (2024)
Cell Reports, 2024 Oct 22; Volume 43, Issue 10, 114813. PubMed ID: 38313299
Duc Nguyen, Garret Wang, Talah Wafa, Tracy Fitzgerald, Yi Gu#
A consistent map in the medial entorhinal cortex supports spatial memory (2024)
Nature Communications, 2024 Feb 17;15(1):1457. PubMed ID: 38368457
Taylor Malone*, NaiWen Tien*, Yan Ma*, Lian Cui, Shangru Lyu, Garret Wang, Duc Nguyen, Kai Zhang, Maxym Myroshnychenko, Jean Tyan, Joshua Gordon, David Kupferschmidt, Yi Gu#
Visual cue-related activity of cells in the medial entorhinal cortex during navigation in virtual reality (2020)
Elife, 2020 Mar 9. PubMed ID: 32149601
Kinkhabwala AA*#, Gu Y*#, Aronov D, Tank DW#
A map-like micro-organization of grid cells of the medial entorhinal cortex (2018)
Cell, 175(3), 736-750
Yi Gu#, Sam Lewallen, Amina A. Kinkhabwala, Cristina Domnisoru, Kijung Yoon, Jeffrey L Gauthier, Ila R. Fiete, David W. Tank#
Differential vesicular sorting of AMPA and GABAA receptors (2016)
Proceedings of the National Academy of Sciences, 113(7):E922-31
Yi Gu, Shu-Ling Chiu*, Pei-Hsun Wu*, Bian Liu*, Michael Delannoy, Da-Ting Lin, Denis Wirtz, and Richard L. Huganir#
Identification of the SNARE complex mediating the exocytosis of NMDA receptors (2016)
Proceedings of the National Academy of Sciences, 113(43): 12280-12285
Yi Gu, Richard L. Huganir#
Cellular resolution optical access to brain regions in fissures: Imaging medial prefrontal cortex and grid cells in entorhinal cortex (2015)
Proceedings of the National Academy of Sciences, 111(52):18739-18744
Ryan J. Low*, Yi Gu*, and David W. Tank#
* Equal contribution， # Corresponding author