Headshot of Yi Gu

Yi Gu, Ph.D.

Investigator
Address
Spatial Navigation and Memory Unit

BG 35 RM 1C-1004

35 CONVENT DR
BETHESDA MD 20814

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.

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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:
(1) How is spatial information represented and computed in the MEC circuit?
(2) Whether and how is spatial memory encoded in the MEC?
(3) How does the MEC interact with other brain areas to perform its function?
(4) 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.

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! Visit the Lab Webpage.

 In vivo two-photon imaging of the MEC during mouse’s virtual navigation (modified from Gu et al., 2018).
Figure 1. In vivo two-photon imaging of the MEC during mouse’s virtual navigation (modified from Gu et al., 2018).
Left: we gain cellular-resolution optical access to the MEC (green area) through a microprism, which is surgically inserted into the transverse fissure and reflects the optical path at 90o.
Right: neural dynamics of the MEC is measured when a mouse navigates in virtual reality. The mouse’s motion in a virtual environment is driven by its running on a ball.
Figure 2. Mouse’s view of a virtual linear track
Figure 2. Mouse’s view of a virtual linear track
Video 1. Mouse’s view during the navigation on the virtual reality track in Figure 2.

 

Figure 3. Neurons in layer 2 of the MEC, which expressed genetically encoded calcium indicator GCaMP6f.
Figure 3. Neurons in layer 2 of the MEC, which expressed genetically encoded calcium indicator GCaMP6f.

Video 2. Calcium dynamics of MEC neurons in Figure 3 when a mouse navigated in virtual reality.

 Postdocs


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Dr. Nai-Wen Tien

Dr. Nai-Wen Tien

Nai-Wen received her Ph.D. for work on function and development of mouse retinal circuits in Dr. Daniel Kerschensteiner’s lab at Washington University in St. Louis. Afterwards she transitioned to system neuroscience and joined Dr. Shaul Druckmann’s lab at Stanford University, working on several collaborative projects studying brain-wide activity for short-term memory. As a human being with terrible sense of direction, Nai-Wen always wonders if she has dysfunctional brain circuits for spatial navigation. To understand the potential reasons for her impaired internal GPS system, she joins Dr. Gu Yi’s lab working on the mechanisms underlying spatial learning and memory. Apart from working on research projects, she enjoys playing board games (especially Betrayal at House on the Hill!) and plans to finish a best-selling Sci-Fi novel about neuroscience.

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Dr. Taylor Malone

Dr. Taylor Malone

Taylor received his B.S. in Biology and Biomedical Engineering Systems from Tufts University, before beginning his Ph.D. in Molecular and Cellular Physiology at Yale University in the laboratory of Leonard Kaczmarek. In the Kaczmarek lab, Taylor studied Slack potassium channels and their gain-of-function mutations leading to childhood epilepsy and intellectual disability. Taylor characterized a novel mechanism by which activation, or gain-of-function mutation, of Slack channels regulates mRNA translation. In the Gu lab, Taylor is pursuing his interest in understanding the mechanisms behind neurological disease by studying the role of the medial entorhinal cortex (MEC) in spatial learning and memory and MEC dysfunction in Alzheimer’s disease. Taylor’s hobbies include hiking, baking, and reading science fiction.

 

Postbacs


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Duc Nguyen

Duc Nguyen

Duc received Bachelor's degree in Psychology from the University of California Berkeley. He joined the lab in August 2020 and is currently working on how sensory information is represented in the medial entorhinal cortex (MEC) during spatial navigation. He's leaving the lab in August 2022 for NYU where he will begin his PhD in Neuroscience.

 

 

 

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Garret Wang

Garret Wang

Garret has a bachelor's degree in biology from the University of California, San Diego. He joined the lab in June 2022 to study spatial processing neural networks in mice within virtual environments. While working with Yi Gu, he plans to foster the skills necessary for careers in research and medicine. In his free time, Garret enjoys music, reading, and creative writing.

 

 

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Jean Tyan

Jean Tyan

Jean received her M.H.S. in Epidemiology from the Johns Hopkins Bloomberg School of Public Health, where she investigated relationships between discriminatory experiences, epigenetic aging, and dementia under the guidance of Dr. Aisha Dickerson. Prior to this, she earned her B.S. in Biology and Biopsychology, Cognition, and Neuroscience from the University of Michigan. There, she studied the role of pre-sleep behaviors in sleep quality and sleep physiology in the lab of Dr. Ada Eban-Rothschild. In the Gu lab, she will join Taylor Malone in examining the dysfunction of the medial entorhinal cortex in Alzheimer's disease. Jean intends to pursue a Ph.D. to bridge basic science and population-level epidemiologic findings to alleviate health disparities in Alzheimer's disease. Outside the lab, she loves to play the flute and enjoys classical music.

 

Alumni


  • Lian Cui (lab manager)
  • Shangru Lyu (postdoc): Scientist, Moderna

1) Amina A. Kinkhabwala*, Yi Gu*, Dmitriy Aronov, David W. Tank (2020)

Visual cue-related activity of cells in the medial entorhinal cortex during navigation in virtual reality, Elife, 2020 Mar 9;9. pii: e43140., doi: 10.7554/eLife.43140. (* Equal contribution)

2) Yi Gu, Sam Lewallen, Amina A. Kinkhabwala, Cristina Domnisoru, Kijung Yoon, Jeffrey L Gauthier, Ila R. Fiete, David W. Tank (2018)

A map-like micro-organization of grid cells of the medial entorhinal cortex, Cell, 175(3), 736-750

3) Yi Gu, Shu-Ling Chiu, Pei-Hsun Wu, Bian Liu, Michael Delannoy, Da-Ting Lin, Denis Wirtz, and Richard L. Huganir (2016)

Differential vesicular sorting of AMPA and GABAA receptors, Proceedings of the National Academy of Sciences, 113(7):E922-31

4) Yi Gu, Richard L. Huganir (2016)

Identification of the SNARE complex mediating the exocytosis of NMDA receptors, Proceedings of the National Academy of Sciences, 113(43): 12280-12285

5) Ryan J. Low*, Yi Gu*, and David W. Tank (2015)

Cellular resolution optical access to brain regions in fissures: Imaging medial prefrontal cortex and grid cells in entorhinal cortex, Proceedings of the National Academy of Sciences, 111(52):18739-18744, (* Equal contribution)