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Dwight Bergles

Dwight Bergles

· Professor of Neuroscience, Biomedical Engineering and Otolaryngology-Head & Neck SurgeryVerified

Johns Hopkins University · Neurosciences

Active 1992–2026

h-index93
Citations36.4k
Papers305130 last 5y
Funding$58.2M3 active
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About

Dwight Bergles is a Professor of Neuroscience, Biomedical Engineering, and Otolaryngology-Head & Neck Surgery at the Johns Hopkins School of Medicine, within the Solomon H. Snyder Department of Neuroscience. His research focuses on understanding the mechanisms of communication between neurons and glial cells, and how these interactions influence brain development, circuit function, and disease. His work employs a diverse range of methods, including transgenic mice, in vivo imaging, and electrophysiological techniques, to explore key areas such as oligodendrocyte precursor cells, myelination, and glial modulation of auditory system development. Bergles' studies aim to define molecular pathways regulating oligodendrogenesis and myelination, investigate how glial-like supporting cells in the cochlea induce neural activity prior to hearing onset, and elucidate the role of astrocytes in neuromodulation and behavior. His contributions advance understanding of neuron-glial communication and its implications for brain development and neurological disorders.

Research topics

  • Neuroscience
  • Medicine
  • Biology
  • Psychology

Selected publications

  • Brain-wide mapping of oligodendrocyte organization, oligodendrogenesis, and myelin injury

    Cell · 2026-02-18 · 1 citations

    articleOpen accessSenior author
  • Myelin is repaired by constitutive differentiation of oligodendrocyte progenitors

    Science · 2026-01-22 · 5 citations

    articleOpen accessSenior author

    Oligodendrocytes form myelin sheaths around axons to enable rapid signaling within neural circuits. The generation of new oligodendrocytes through differentiation of oligodendrocyte precursor cells (OPCs) promotes myelin plasticity and repair in the adult brain. Here, we performed genetic interrogation and in vivo analysis of OPCs in the mouse brain to determine their differentiation dynamics. Our results show that OPCs attempt to differentiate throughout the adult central nervous system with spatial and temporal regularity. The differentiation rate was not influenced by myelin demand or oligodendrocyte loss and declined with age and in response to acute inflammation. The results suggest that OPC differentiation is governed primarily by constitutive processes and might be negatively influenced by aging and inflammation.

  • Astrocyte-induced internal state transitions reshape brainwide sensory, integrative, and motor computations

    bioRxiv (Cold Spring Harbor Laboratory) · 2026-02-05 · 1 citations

    articleOpen access

    Summary Animals rapidly adapt to changing circumstances by shifting how they perceive, integrate, and act. Such flexibility is often attributed to transitions between internal states that exert widespread influence across the brain. Yet the mechanisms that drive state transitions and how they reconfigure brainwide computation remain unclear. Larval zebrafish, when actions are rendered futile by decoupling visual flow feedback from swimming in virtual reality, enter a temporary passive, energy-preserving state. In this state, astrocyte calcium levels are elevated, and swim reinitiation requires greater accumulated visual motion. Using whole-brain, cellular-resolution activity imaging, we observed widespread circuit alterations underlying this disengaged state: neuronal visual responses weakened, visual motion integration over time became dramatically leakier, motor inhibition increased, and motor preparation slowed, together suppressing conversion of sensory evidence into action. Astrocyte calcium rose during futile swimming, tracked the emergence and resolution of these brainwide changes, and was both necessary and sufficient to drive them. Thus, astrocytes orchestrate internal states that profoundly reshape neural computations, most powerfully at intermediate integrative processing stages, to meet changing demands. Highlights Internal state change alters brainwide neuronal processing at every stage of the sensorimotor transformation Effects are most powerful at integrative stages through stimulus memory collapse As state resolves, amplification of sensory representations synergizes with reduced motor inhibition for action reinitiation Astrocyte activity drives these brainwide adaptive shifts in neuronal dynamics

  • Conservation of Neuron‐Astrocyte Correlated Activity in Developing Sensory Pathways

    Glia · 2026-03-26

    articleOpen accessSenior author

    Neurons in developing sensory organs exhibit prolonged burst firing before the onset of sensory experience. This activity promotes neuronal survival and maturation in central sensory pathways. Within the auditory system, periodic bursts of synaptic glutamate release activate metabotropic glutamate receptors (mGluRs) on astrocytes, resulting in spatially and temporally correlated calcium transients; however, whether this phenomenon occurs in other sensory modalities is unknown. Using in vivo calcium imaging in the midbrain of awake mouse pups before eyelid opening, we show that retina wave-induced burst firing of visual afferents induces correlated waves of astrocyte activity in the superior colliculus (SC), a visual processing region. Glutamate sensor imaging revealed that each neuronal burst resulted in glutamate transients at astrocyte membranes in both developing sensory regions. Calcium transients in SC astrocytes resulted from activation of astrocytic mGluR5 and mGluR3, similar to astrocyte events in the nearby inferior colliculus (IC), which are induced by neuronal burst firing in the cochlea. Astrocyte calcium increased with each neuronal wave in the SC, but only the largest neuronal events triggered astrocyte responses in the IC. Astrocyte transcriptomic analysis suggested differential expression of mGluR3 and mGluR5 between these sensory regions, in accordance with the greater dependence on mGluR5 in IC astrocytes. Despite differences in receptor contribution and temporal features of activity, astrocytes in these different regions exhibited similar overall calcium activity. Thus, neuronal burst firing in developing sensory organs provides a conserved mechanism to synchronize neuronal and astrocyte activity in the brain at a critical stage of development.

  • Versatile high-speed volumetric imaging from microscopic to macroscopic scale by self-adaptive oblique plane microscopy

    Research Square · 2026-03-12

    preprintOpen accessSenior author
  • Genetically encoded assembly recorder temporally resolves cellular history

    Nature · 2026-03-03 · 1 citations

    articleOpen access

    Abstract Cells constantly change their molecular state in response to internal and external cues 1 . Mapping cellular activity in tissues with spatiotemporal precision is essential for understanding organ physiology, pathology and regenerative processes. Current cell-sensing modalities primarily rely on either end point analysis that takes static snapshots 2 or real-time sensing that monitors a small subset of cells 3,4 . Here we introduce granularly expanding memory for intracellular narrative integration (GEMINI), an in cellulo recording platform that leverages a computationally designed protein assembly as an intracellular memory device to record the history of individual cells. GEMINI grows predictably within live cells, capturing cellular events as tree-ring-like fluorescent patterns for imaging-based retrospective readout. Absolute chronological information of activity histories is attainable with hour-level accuracy. GEMINI effectively maps differential NF-κB-mediated transcriptional changes, resolving fast dynamics of 15 min and providing quantifiable signal amplitudes. In a xenograft model, GEMINI records inflammation-induced signalling dynamics across tissue, revealing spatial heterogeneity linked to vascular density. When expressed in the mouse brain, GEMINI minimally impacts neuronal functions and can resolve both transcriptional changes and activity patterns of neurons. Together, GEMINI provides a robust and generalizable means for spatiotemporal mapping of cell dynamics underlying physiological and pathological processes in both culture and intact tissues.

  • Flexible ensheathment of axons enables myelination of complex CNS networks

    Nature · 2026-04-01

    articleOpen accessSenior author
  • Genetically encoded assembly recorder temporally resolves cellular histories <i>in cellulo</i> and <i>in vivo</i>

    bioRxiv (Cold Spring Harbor Laboratory) · 2025-07-18

    preprintOpen access

    Abstract Mapping cellular activity with high spatiotemporal precision in complex tissues is essential for understanding organ physiology, pathology, and regenerative processes. Here, we introduce G ranularly E xpanding M emory for I ntracellular N arrative I ntegration (GEMINI), an in cellulo recording platform that leverages a computationally designed protein assembly as an intracellular memory device to record individual cells’ activity histories. GEMINI grows predictably within live cells with minimal interference to cellular functions, capturing cellular activities as tree-ring-like fluorescent patterns in the expanding scaffolds for imaging-based retrospective readout. Absolute chronological information of activity histories was attainable with hour-level accuracy through the integration of fiducial timestamps. GEMINI effectively resolved differential NFκB-mediated transcriptional changes, distinguishing fast dynamics of 15 minutes, and providing quantifiable signal amplitudes. In a xenograft model, GEMINI recorded inflammation-induced signaling dynamics across tissue with cellular resolution, revealing spatial heterogeneity linked to vascular density. When expressed in the mouse brain, GEMINI exhibited negligible impact on neuronal survival, with animals maintaining normal motor and cognitive behaviors. In physiological contexts, GEMINI successfully resolved both transcriptional changes and activity patterns of neurons in the brain. Together, GEMINI provides a robust and generalizable means for spatiotemporal mapping of cell dynamics underlying physiological and pathological processes in both culture and intact tissues.

  • Spontaneous calcium transients in hair cell stereocilia

    Scientific Reports · 2025-09-29 · 2 citations

    articleOpen access

    Abstract The hair bundle of auditory and vestibular hair cells converts mechanical stimuli into electrical signals through mechanoelectrical transduction (MET). The MET apparatus is built around a tip link that connects neighboring stereocilia that are aligned in the direction of mechanosensitivity of the hair bundle. Upon stimulation, the MET channel complex responds to changes in tip-link tension and allows a cation influx into the cell. Ca 2+ influx in stereocilia has been used as a signature of MET activity. Using genetically encoded Ca 2+ sensors (GCaMP3, GCaMP6s) and high-performance fluorescence confocal microscopy, we detect spontaneous Ca 2+ transients in individual stereocilia in developing and fully formed hair bundles. We demonstrate that this activity is abolished by MET channel blockers and thus likely originates from putative MET channels. We observe Ca 2+ transients in the stereocilia of mice in tissue explants as well as in vivo in zebrafish hair cells, indicating this activity is evolutionarily conserved. Within stereocilia, the origin of Ca 2+ transients is not limited to the canonical MET site at the stereocilia tip but is also present along the stereocilia length. Remarkably, we also observe these Ca 2+ transients in the microvilli-like structures on the hair cell surface in the early stages of bundle development, prior to the onset of MET. Ca 2+ transients are also present in the tallest rows of stereocilia in auditory hair cells, structures not traditionally thought to contain MET channels. We hypothesize that this newly described activity may reflect stochastic and spontaneous MET channel opening. Localization of these transients to other regions of the stereocilia indicates the presence of a pool of channels or channel precursors. Our work provides insights into MET channel assembly, maturation, function, and turnover. .

  • Versatile high-speed volumetric imaging from microscopic to macroscopic scale by self-adaptive oblique plane microscopy

    bioRxiv (Cold Spring Harbor Laboratory) · 2025-12-18 · 1 citations

    preprintOpen access

    Abstract There is an increasing need for large-scale high-speed volumetric recording in complex multi-cellular model systems to define dynamic processes. Oblique plane microscopy (OPM) provides a solution that features oblique illumination, rapid optical scanning, and remote focusing to achieve real-time 4D microscopy. OPM implements light sheet imaging via a single primary objective lens, making the entire space below the objective accessible for large specimens, such as living mouse brain. Yet it is challenging to adopt OPM beyond a microscopic scale ( i.e. size &lt; 1mm), limiting its broad applications. Here we present a self-adaptive OPM that leverages Abbe’s sine condition to unlock its flexibility across a range of field-of-views (FOVs) (up to 8 mm 2 ) and resolutions (down to 2.2 µm 3 ). This versatility enables brain-wide single neuron volumetric calcium imaging in behaving larval zebrafish (1×0.4 mm 2 FOV at 5 Hz) and capillary blood cell tracking in living mouse brain (&gt;3×3 mm 2 FOV) with a sweeping 0.32 mm wide volume section at 100 Hz. In optically cleared mouse brain, the flexibility allows a screen-and-zoom capability by sequentially imaging the whole brain at low-and-high magnifications to locate and resolve subcellular structures such as dendritic tress and spines. By offering a switchable imaging resolution, volume, and speed, the self-adaptive OPM achieves a versatile platform for studying a wide range of multi-cellular model system, whether in vivo or fixed and optically cleared.

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Education

  • Ph.D., Neuroscience

    Johns Hopkins University

    1990
  • B.S., Biology

    University of California, San Diego

    1984
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