About

Dr. Hey-Kyoung Lee is a professor of neuroscience at the Johns Hopkins University School of Medicine. Her research focuses on the cellular and molecular changes that occur at synapses to enable memory storage. Her laboratory aims to elucidate the mechanisms underlying cross-modal synaptic plasticity and to expose the events that occur in diseased brains, such as in Alzheimer's disease. She combines techniques such as electrophysiological recording, biochemical/molecular analysis, and imaging to understand the cellular and molecular changes during synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD). Her work includes examining molecular and cellular mechanisms of global homeostatic synaptic plasticity using sensory cortices as model systems, and investigating how sensory loss, such as vision loss, triggers changes in synaptic transmission that may underlie sensory compensation. Dr. Lee's research also involves analyzing alterations in synaptic plasticity mechanisms in mouse models of Alzheimer's disease, in collaboration with other researchers at Johns Hopkins.

Research topics

• Artificial Intelligence
• Psychology
• Computer Science
• Neuroscience
• Cognitive psychology
• Biology
• Physics

Selected publications

• Rapid plasticity of default-mode local network architectures following adult-onset blindness

  Mendeley Data · 2026-01-01

  datasetOpen access1st authorCorresponding

  Data for Mesik et al. paper.

  PublisherDOI

• Rapid plasticity of default-mode local network architectures following adult-onset blindness

  Open MIND · 2026-01-01

  dataset1st authorCorresponding

  Data for Mesik et al. paper.

  DOI

• Rapid plasticity of default-mode local network architectures following adult-onset blindness

  Cell Reports · 2026-01-01 · 2 citations

  articleOpen accessSenior author

  Sensory cortices are not silent in the absence of sensory inputs but generate spontaneous activity intrinsic to the cortical circuit referred to as default-mode activity. Here, we report that spontaneous activity of excitatory and inhibitory neuronal types in layer 2/3 of the adult primary visual cortex (V1) exhibits quite stable default-mode local network architectures, which undergo rapid and selective restructuring following bilateral enucleation (EN), a model of adult-onset blindness. Spontaneous activity of both pyramidal (Pyr) and parvalbumin (PV) neurons rapidly and persistently increased following EN, but the default-mode network architecture of only Pyr rapidly rearranged and stabilized. Vasoactive intestinal peptide (VIP) neuronal network also restructured rapidly after EN, but their spontaneous activity increase was delayed. Somatostatin (SOM) neuronal network was quite stable. Our results indicate that adult-onset blindness rapidly and selectively modifies the stable default-mode local network architectures of V1, independent of increases in spontaneous activity, reflecting rapid adaptation to vision loss.

  PublisherDOI

• Editorial overview: Introduction to neurobiology of learning and plasticity

  Current Opinion in Neurobiology · 2025-08-27

  editorialSenior author
  PublisherDOI

• Spatial Mapping of Activity Changes across Sensory Areas Following Visual Deprivation in Adults

  Journal of Neuroscience · 2024-11-26 · 3 citations

  articleOpen accessSenior author

  Loss of a sensory modality triggers global adaptation across brain areas, allowing the remaining senses to guide behavior more effectively. There are specific synaptic and circuit plasticity observed across many sensory areas, which suggests potential widespread changes in activity. Here we used a cFosTRAP2 mouse line to drive tdTomato (tdT) expression in active cells to spatially map the extent of activity changes in various sensory areas in adult mice of both sexes following two modes of visual deprivation. We found that in the primary visual cortex (V1), both dark exposure (DE) and enucleation (EN) caused an initial loss of active cells followed by a partial rebound, which occurred relatively more in the superficial layers. A similar pattern was observed in the secondary visual cortex, especially in the lateral areas (V2L). The spared primary sensory cortices adapted distinctly. In the primary somatosensory barrel cortex (S1BF), there was a change in the density of active cells dependent on the duration and the mode of visual deprivation. In the primary auditory cortex (A1), there was a relative reduction in the density of active cells in the superficial layers without a significant change in the overall density. There were minimal changes in the active cell density in the secondary cortices of the spared senses and the multisensory retrosplenial cortex (RSP). Our results are consistent with cross-modal recruitment of the deprived visual cortex and compensatory plasticity in the spared primary sensory cortices that can support enhanced processing and refinement of the spared senses.

  PublisherOA PDFDOI

• H-Ras induces exuberant de novo dendritic protrusion growth in mature neurons regardless of cell type

  iScience · 2024-07-18 · 2 citations

  articleOpen access

  spine formation in mature H-Ras expressing neurons, suggesting H-Ras's effect is not limited to early development. In PyNs and PV-INs, but not VIP-INs, spine neck lengths shifted to filopodia-like phenotypes. H-Ras primarily induced filopodia in PyNs and spines in PV- and VIP-INs. Increased protrusions in H-Ras-transfected PyNs lacked key excitatory synaptic proteins and did not affect miniature excitatory postsynaptic currents (mEPSCs), suggesting multifaceted roles beyond excitatory synapses.

  PublisherDOI

• Dark exposure reduces high-frequency hearing loss in C57BL/6J mice

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-05-03 · 1 citations

  preprintOpen access

  Summary Plastic changes in the brain are primarily limited to early postnatal periods. Recovery of adult brain plasticity is critical for the effective development of therapies. A brief (1-2 week) duration of visual deprivation (dark exposure, DE) in adult mice can trigger functional plasticity of thalamocortical and intracortical circuits in the primary auditory cortex suggesting improved sound processing. We tested if DE enhances the ability of adult mice to detect sounds. We trained and continuously evaluated the behavioral performance of mice in control and DE conditions using automated home-cage training. Consistent with age-related peripheral hearing loss present in C57BL/6J mice, we observed decreased performance for high-frequency sounds with age, which was reduced by DE. In CBA mice with preserved peripheral hearing, we also found that DE enhanced auditory performance in low and mid frequencies over time compared to the control.

  PublisherOA PDFDOI

• Transcranial Low-Intensity Focused Ultrasound Stimulation of the Visual Thalamus Produces Long-Term Depression of Thalamocortical Synapses in the Adult Visual Cortex

  Journal of Neuroscience · 2024-02-05 · 16 citations

  articleOpen accessSenior author

  Transcranial focused ultrasound stimulation (tFUS) is a noninvasive neuromodulation technique, which can penetrate deeper and modulate neural activity with a greater spatial resolution (on the order of millimeters) than currently available noninvasive brain stimulation methods, such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). While there are several studies demonstrating the ability of tFUS to modulate neuronal activity, it is unclear whether it can be used for producing long-term plasticity as needed to modify circuit function, especially in adult brain circuits with limited plasticity such as the thalamocortical synapses. Here we demonstrate that transcranial low-intensity focused ultrasound (LIFU) stimulation of the visual thalamus (dorsal lateral geniculate nucleus, dLGN), a deep brain structure, leads to NMDA receptor (NMDAR)-dependent long-term depression of its synaptic transmission onto layer 4 neurons in the primary visual cortex (V1) of adult mice of both sexes. This change is not accompanied by large increases in neuronal activity, as visualized using the cFos Targeted Recombination in Active Populations (cFosTRAP2) mouse line, or activation of microglia, which was assessed with IBA-1 staining. Using a model (SONIC) based on the neuronal intramembrane cavitation excitation (NICE) theory of ultrasound neuromodulation, we find that the predicted activity pattern of dLGN neurons upon sonication is state-dependent with a range of activity that falls within the parameter space conducive for inducing long-term synaptic depression. Our results suggest that noninvasive transcranial LIFU stimulation has a potential for recovering long-term plasticity of thalamocortical synapses in the postcritical period adult brain.

  PublisherOA PDFDOI

• Brief periods of visual deprivation in adults increase performance on auditory tasks

  iScience · 2024-09-21 · 4 citations

  articleOpen access

  Plastic changes in the brain are primarily limited to early postnatal periods. Recovery of adult brain plasticity is critical for the effective development of therapies. A brief (1-2 weeks) duration of visual deprivation (dark exposure, DE) in adult mice can trigger functional plasticity of thalamocortical and intracortical circuits in the primary auditory cortex suggesting improved sound processing. We tested if DE enhances the ability of adult mice to detect sounds. We trained and continuously evaluated the behavioral performance of mice in control and DE conditions using automated home-cage training. Consistent with age-related peripheral hearing loss present in C57BL/6J mice, we observed decreased performance for high-frequency sounds with age, which was reduced by DE. In CBA mice with preserved peripheral hearing, we also found that DE showed modest auditory performance improvements in low and mid frequencies over time compared to the control.

  PublisherDOI

• Mouse models of <i>SYNGAP1</i> -related intellectual disability

  Proceedings of the National Academy of Sciences · 2023-09-05 · 17 citations

  articleOpen access

  SYNGAP1 is a Ras-GTPase-activating protein highly enriched at excitatory synapses in the brain. De novo loss-of-function mutations in SYNGAP1 are a major cause of genetically defined neurodevelopmental disorders (NDDs). These mutations are highly penetrant and cause SYNGAP1 -related intellectual disability (SRID), an NDD characterized by cognitive impairment, social deficits, early-onset seizures, and sleep disturbances. Studies in rodent neurons have shown that Syngap1 regulates developing excitatory synapse structure and function, and heterozygous Syngap1 knockout mice have deficits in synaptic plasticity, learning, and memory and have seizures. However, how specific SYNGAP1 mutations found in humans lead to disease has not been investigated in vivo. To explore this, we utilized the CRISPR-Cas9 system to generate knock-in mouse models with two distinct known causal variants of SRID: one with a frameshift mutation leading to a premature stop codon, SYNGAP1; L813RfsX22, and a second with a single-nucleotide mutation in an intron that creates a cryptic splice acceptor site leading to premature stop codon, SYNGAP1; c.3583-9G&gt;A . While reduction in Syngap1 mRNA varies from 30 to 50% depending on the specific mutation, both models show ~50% reduction in Syngap1 protein, have deficits in synaptic plasticity, and recapitulate key features of SRID including hyperactivity and impaired working memory. These data suggest that half the amount of SYNGAP1 protein is key to the pathogenesis of SRID. These results provide a resource to study SRID and establish a framework for the development of therapeutic strategies for this disorder.

  PublisherOA PDFDOI

Recent grants

• Reversible activation of critical period plasticity in visual cortex

  NIH · $3.6M · 2015–2025

• NIH Grant R21NS070645

  NIH · $409k · 2013

• Global Synpatic Plasticity Mechanisms in Visual Cortex

  NIH · $7.9M · 2004–2030

• NIH Grant R01EY022720

  NIH · $2.1M · 2019

Frequent coauthors

• Richard L. Huganir

  Johns Hopkins Medicine

  67 shared

• Alfredo Kirkwood

  Johns Hopkins University

  55 shared

• Bryce D. Grier

  Allen Institute for Brain Science

  38 shared

• Gabrielle Ewall

  Johns Hopkins Medicine

  36 shared

• Lukas Mesik

  Johns Hopkins Medicine

  28 shared

• Patrick O. Kanold

  Johns Hopkins University

  28 shared

• Samuel Parkins

  Johns Hopkins University

  27 shared

• Ming Gao

  26 shared

Education

• Ph.D., Neuroscience

  Brown University

  1997

• B.S., Biology

  Yonsei University

  1992

Awards & honors

• The Sloan Research Fellowship in 2004
• Junior Faculty Award from the College of Chemical and Life S…
• nominated as one of the "Yonsei 100 Women Leaders" in 2006