About

Kenneth Wong is the Walter and Lenore Annenberg Professor of Education Policy, as well as a Professor of International and Public Affairs and a Professor of Political Science at Brown University. He is associated with the Brown University China Initiative. His work focuses on education policy, international affairs, and political science, contributing to research and academic discourse in these fields. Further details about his specific research interests, background, and key contributions are not provided in the available page text.

Research topics

• Neuroscience
• Biology
• Cell biology
• Computer science
• Anatomy

Selected publications

• Label-free photoacoustic computed tomography of visually evoked responses in the primary visual cortex and four subcortical retinorecipient nuclei of anesthetized mice

  Neurophotonics · 2024-07-30

  articleOpen access

  SignificanceMany techniques exist for screening retinal phenotypes in mouse models in vision research, but significant challenges remain for efficiently probing higher visual centers of the brain. Photoacoustic computed tomography (PACT), with optical sensitivity to hemodynamic response (HR) in brain and ultrasound resolution, provides unique advantages in comprehensively assessing higher visual function in the mouse brain.AimWe aim to examine the reliability of PACT in the functional phenotyping of mouse models for vision research.ApproachA PACT-ultrasound (US) parallel imaging system was established with a one-dimensional (1D) US transducer array and a tunable laser. Imaging was performed at three coronal planes of the brain, covering the primary visual cortex and the four subcortical nuclei, including the superior colliculus, the dorsal lateral geniculate nucleus, the suprachiasmatic nucleus, and the olivary pretectal nucleus. The visual-evoked HR was isolated from background signals using an impulse-based data processing protocol. rd1 mice with rod/cone degeneration, melanopsin-knockout (mel-KO) mice with photoreceptive ganglion cells that lack intrinsic photosensitivity, and wild-type mice as controls were imaged. The quantitative characteristics of the visual-evoked HR were compared.ResultsQuantitative analysis of the HRs shows significant differences among the three mouse strains: (1) rd1 mice showed both smaller and slower responses compared with wild type (n=10,10, p<0.01) and (2) mel-KO mice had lower amplitude but not significantly delayed photoresponses than wild-type mice (n=10,10, p<0.01). These results agree with the known visual deficits of the mouse strains.ConclusionsPACT demonstrated sufficient sensitivity to detecting post-retinal functional deficits.

  PublisherOA PDFDOI

• Photoacoustic imaging of visually evoked cortical and subcortical hemodynamic activity in mouse brain: feasibility study with piezoelectric and capacitive micromachined ultrasonic transducer (CMUT) arrays

  Biomedical Optics Express · 2023-10-31 · 3 citations

  articleOpen access

  This study investigates the feasibility of capturing visually evoked hemodynamic responses in the mouse brain using photoacoustic tomography (PAT) and ultrasound (US) dual-modality imaging. A commercial piezoelectric transducer array and a capacitive micromachined ultrasonic transducer (CMUT) array were compared using a programmable PAT-US imaging system. The system resolution was measured by imaging phantoms. We also tested the ability of the system to capture visually evoked hemodynamic responses in the superior colliculus as well as the primary visual cortex in wild-type mice. Results show that the piezoelectric transducer array and the CMUT array exhibit comparable imaging performance, and both arrays can capture visually evoked hemodynamic responses in subcortical as well as cortical regions of the mouse brain.

  PublisherDOI

• S-Cone Photoreceptors Regulate Daily Rhythms and Light-Induced Arousal/Wakefulness in Diurnal Grass Rats ( <i>Arvicanthis niloticus</i> )

  Journal of Biological Rhythms · 2023-05-24 · 7 citations

  articleOpen accessCorresponding

  Beyond visual perception, light has non-image-forming effects mediated by melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs). The present study first used multielectrode array recordings to show that in a diurnal rodent, Nile grass rats ( Arvicanthis niloticus), ipRGCs generate rod/cone-driven and melanopsin-based photoresponses that stably encode irradiance. Subsequently, two ipRGC-mediated non-image-forming effects, namely entrainment of daily rhythms and light-induced arousal, were examined. Animals were first housed under a 12:12 h light/dark cycle (lights-on at 0600 h) with the light phase generated by a low-irradiance fluorescent light (F12), a daylight spectrum (D65) stimulating all photoreceptors, or a narrowband 480 nm spectrum (480) that maximized melanopsin stimulation and minimized S-cone stimulation (λ max 360 nm) compared to D65. Daily rhythms of locomotor activities showed onset and offset closer to lights-on and lights-off, respectively, in D65 and 480 than in F12, and higher day/night activity ratio under D65 versus 480 and F12, suggesting the importance of S-cone stimulation. To assess light-induced arousal, 3-h light exposures using 4 spectra that stimulated melanopsin equally but S-cones differentially were superimposed on F12 background lighting: D65, 480, 480 + 365 (narrowband 365 nm), and D65 − 365. Compared to the F12-only condition, all four pulses increased in-cage activity and promoted wakefulness, with 480 + 365 having the greatest and longest-lasting wakefulness-promoting effects, again indicating the importance of stimulating S-cones as well as melanopsin. These findings provide insights into the temporal dynamics of photoreceptor contributions to non-image-forming photoresponses in a diurnal rodent that may help guide future studies of lighting environments and phototherapy protocols that promote human health and productivity.

  PublisherOA PDFDOI

• Adeno-associated virus (AAV)-mediated Cre recombinase expression in melanopsin ganglion cells without leaky expression in rod/cone photoreceptors

  Journal of Neuroscience Methods · 2022-12-05 · 2 citations

  articleOpen accessSenior authorCorresponding

  Constituting about 5 % of mouse retinal ganglion cells (RGCs), intrinsically photosensitive retinal ganglion cells (ipRGCs) express the photopigment melanopsin (gene symbol Opn4) and drive such photoresponses as pupil constriction, melatonin suppression, and circadian photoentrainment. Opn4Cre mice with Cre recombinase-expressing ipRGCs have enabled genetic manipulation of ipRGCs; unfortunately, while Cre expression within the inner retina is ipRGC-specific, leaky expression also occurs in some outer retinal photoreceptors, so Cre-induced alterations in the latter cells may confound certain studies of ipRGC function. Methods that express Cre in ipRGCs but not rods or cones are needed. New Method: We have constructed a recombinant serotype-2 adeno-associated virus, rAAV2-Opn4-Cre, with the improved Cre recombinase (iCre) gene under the control of a ∼3kbp Opn4 promoter sequence, and injected it intravitreally into mice to transduce inner retinal neurons while sparing the outer retina. We introduced rAAV2-Opn4-Cre into Cre reporter mice in which enhanced green fluorescent protein (EGFP) expression indicates Cre expression. Single-cell electrophysiological recordings and intracellular dye fills showed that 84 % of the EGFP+ cells were ipRGCs including M1–M6 types, while 16 % were conventional RGCs. Comparison with Existing Methods: Whereas Opn4Cre mice express Cre in some rod/cone photoreceptors, intravitreally applied rAAV2-Opn4-Cre induces Cre only in the inner retina, albeit with leaky expression in some conventional RGCs. rAAV2-Opn4-Cre has overcome a significant limitation of Opn4Cre mice. We recommend usage scenarios where the Cre-expressing conventional RGCs should not pose a problem.

  PublisherDOI

• Label-free photoacoustic computed tomography of visually-evoked hemodynamic responses in the mouse brain

  2022-03-07

  article

  The current functional brain mapping techniques such as fMRI and DOI suffer from limited spatial resolution. Photoacoustic (PA) imaging combines the sensitivity of optical imaging to hemodynamic variations, and spatial resolution of ultrasound detection. In this study, we built a label-free PA computed tomography (PACT) system with a ring-shaped ultrasound array to monitor the hemodynamic changes in the primary visual cortex (V1) of mice in response to retinal photostimulation. The responses of wild-type and retinal degenerate (rd1) mice were compared. A linear-array PACT system was also used to measure the visually-evoked subcortical responses. Therefore, PACT is potential tool to study the effect of retinal degeneration of mice on the visual pathway.

  PublisherDOI

• Circadian Responses to Light-Flash Exposure: Conceptualization and New Data Guiding Future Directions

  Frontiers in Neurology · 2021-02-11 · 14 citations

  articleOpen access1st authorCorresponding

  A growing number of studies document circadian phase-shifting after exposure to millisecond light flashes. When strung together by intervening periods of darkness, these stimuli evoke pacemaker responses rivaling or outmatching those created by steady luminance, suggesting that the circadian system's relationship to light can be contextualized outside the principle of simple dose-dependence. In the current review, we present a brief chronology of this work. We then develop a conceptual model around it that attempts to relate the circadian effects of flashes to a natural integrative process the pacemaker uses to intermittently sample the photic information available at dawn and dusk. Presumably, these snapshots are employed as building blocks in the construction of a coherent representation of twilight the pacemaker consults to orient the next day's physiology (in that way, flash-resetting of pacemaker rhythms might be less an example of a circadian visual illusion and more an example of the kinds of gestalt inferences that the image-forming system routinely makes when identifying objects within the visual field; i.e., closure). We conclude our review with a discussion on the role of cones in the pacemaker's twilight predictions, providing new electrophysiological data suggesting that classical photoreceptors-but not melanopsin-are necessary for millisecond, intermediate-intensity flash responses in ipRGCs (intrinsically photosensitive retinal ganglion cells). Future investigations are necessary to confirm this "Cone Sentinel Model" of circadian flash-integration and twilight-prediction, and to further define the contribution of cones vs. rods in transducing pacemaker flash signals.

  PublisherOA PDFDOI

• The effect of axon trajectory on retinal ganglion cell activation with epiretinal stimulation

  2021-05-04 · 2 citations

  articleOpen access

  For epiretinal prostheses, disc electrodes stimulate retinal ganglion cells (RGCs) with electric current to create visual percepts. Prior studies have determined that the sodium channel band (SOCB), located on the RGC axon (30-50 μm from the soma), is the most sensitive site to extracellular stimulation because of its high sodium channel density. Biophysical cable models used to study RGC activation in silico often rely on simplified axon trajectories, disregarding the non-uniform paths that axons follow to the optic disc. However, since axonal activation is a critical mechanism in epiretinal stimulation, it is important to investigate variable RGC axon trajectories. In this study, we use a computational model to perform a sensitivity analysis examining how the morphometry of an RGC axon affects predictions of retinal activation. We determine that RGC cable models are sensitive to changes in the ascending axon trajectory between the soma and nerve fiber layer. On the other hand, RGC cable models are relatively robust to trajectory deviations in the plane parallel to the disc electrode's surface. Overall, our results suggest that incorporating natural variations of soma depth and nerve fiber layer entry angle could result in a more realistic model of the retina's response to epiretinal stimulation and a better understanding of elicited visual percepts.

  PublisherOA PDFDOI

• Label-free in vivo Photoacoustic Imaging of Mouse Cortical Responses to Visual Stimulation

  2021-08-23

  article

• M1-Type, but Not M4-Type, Melanopsin Ganglion Cells Are Physiologically Tuned to the Central Circadian Clock

  Frontiers in Neuroscience · 2021-05-06 · 11 citations

  articleOpen access

  Proper circadian photoentrainment is crucial for the survival of many organisms. In mammals, intrinsically photosensitive retinal ganglion cells (ipRGCs) can use the photopigment melanopsin to sense light independently from rod and cone photoreceptors and send this information to many brain nuclei such as the suprachiasmatic nucleus (SCN), the site of the central circadian pacemaker. Here, we measure ionic currents and develop mathematical models of the electrical activity of two types of ipRGCs: M1, which projects to the SCN, and M4, which does not. We illustrate how their ionic properties differ, mainly how ionic currents generate lower spike rates and depolarization block in M1 ipRGCs. Both M1 and M4 cells have large geometries and project to higher visual centers of the brain via the optic nerve. Using a partial differential equation model, we show how axons of M1 and M4 cells faithfully convey information from the soma to the synapse even when the signal at the soma is attenuated due to depolarization block. Finally, we consider an ionic model of circadian photoentrainment from ipRGCs synapsing on SCN neurons and show how the properties of M1 ipRGCs are tuned to create accurate transmission of visual signals from the retina to the central pacemaker, whereas M4 ipRGCs would not evoke nearly as efficient a postsynaptic response. This work shows how ipRGCs and SCN neurons' electrical activities are tuned to allow for accurate circadian photoentrainment.

  PublisherOA PDFDOI

• Amacrine Cells Forming Gap Junctions With Intrinsically Photosensitive Retinal Ganglion Cells: ipRGC Types, Neuromodulator Contents, and Connexin Isoform

  Investigative Ophthalmology & Visual Science · 2021-01-07 · 26 citations

  articleOpen accessSenior authorCorresponding

  Purpose: Intrinsically photosensitive retinal ganglion cells (ipRGCs) signal not only centrally to non-image-forming visual centers of the brain but also intraretinally to amacrine interneurons through gap junction electrical coupling, potentially modulating image-forming retinal processing. We aimed to determine (1) which ipRGC types couple with amacrine cells, (2) the neuromodulator contents of ipRGC-coupled amacrine cells, and (3) whether connexin36 (Cx36) contributes to ipRGC-amacrine coupling. Methods: Gap junction-permeable Neurobiotin tracer was injected into green fluorescent protein (GFP)-labeled ipRGCs in Opn4Cre/+; Z/EG mice to stain coupled amacrine cells, and immunohistochemistry was performed to reveal the neuromodulator contents of the Neurobiotin-stained amacrine cells. We also created Opn4Cre/+; Cx36flox/flox; Z/EG mice to knock out Cx36 in GFP-labeled ipRGCs and looked for changes in the number of ipRGC-coupled amacrine cells. Results: Seventy-three percent of ipRGCs, including all six types (M1-M6), were tracer-coupled with amacrine somas 5.7 to 16.5 µm in diameter but not with ganglion cells. Ninety-two percent of the ipRGC-coupled somas were in the ganglion cell layer and the rest in the inner nuclear layer. Some ipRGC-coupled amacrine cells were found to accumulate serotonin or to contain nitric oxide synthase or neuropeptide Y. Knocking out Cx36 in M2 and M4 dramatically reduced the number of coupled somas. Conclusions: Heterologous gap junction coupling with amacrine cells is widespread across mouse ipRGC types. ipRGC-coupled amacrine cells probably comprise multiple morphologic types and use multiple neuromodulators, suggesting that gap junctional ipRGC-to-amacrine signaling likely exerts diverse modulatory effects on retinal physiology. ipRGC-amacrine coupling is mediated partly, but not solely, by Cx36.

  PublisherDOI

Recent grants

• NIH Grant R00EY018863

  NIH · $700k · 2013

• Retrograde Signaling by Intrinsically Photosensitive Retinal Ganglion Cells

  NIH · $2.4M · 2013–2022

• NIH Grant F32EY016678

  NIH · $93k · 2007

• NIH Grant K99EY018863

  NIH · $168k · 2010

• Functional Assessment Core

  NIH · $14.4M · 1997–2027

Frequent coauthors

• David M. Berson

  John Brown University

  66 shared

• Dustin M. Graham

  Stony Brook University

  43 shared

• Xiwu Zhao

  Second Hospital of Shandong University

  39 shared

• O. N. Dumitrescu

  Providence College

  25 shared

• Guan Xu

  University of Michigan–Ann Arbor

  24 shared

• Aaron N. Reifler

  University of Michigan–Ann Arbor

  17 shared

• Xueding Wang

  16 shared

• Kai‐Wei Chang

  University of Michigan–Ann Arbor

  16 shared