Electrophysiology
We use single and paired recordings from cells in flat mounted mouse retina to study visual processing. Cells are recorded either in cell-attached mode to measure spike output or in whole cell voltage-clamp mode to reveal synaptic conductances. During recordings we stimulate the retina with patterns of light projected onto the photoreceptors using a custom digital light projection system. Paired recordings measure signal transfer between synaptically-connected cells. In some experiments, we target specific cell types using a fluorescence signal measured with two-photon illumination. We are able to target cells in this manner while maintaining physiological light responses.
Anatomical Circuit Mapping
We are developing new strategies to map the circuitry of the mouse retina at the level of individual synaptic connections between molecularly and physiologically identified cell types. We employ techniques such as targeted RNA manipulations, immunohistochemistry and confocal microscopy to quantify synaptic connectivity.
Computational Modeling
Modeling is a key component of our work as we seek to place our physiological and anatomical measurements in the context of full retinal circuits. We create our own models in the lab, and we collaborate with theorists in other labs. Our modeling efforts fall into two main categories: 1) Models that predict the spike output of retinal ganglion cells (the output cells of the retina) given arbitrary spatiotemporal patterns of light. We use a combination of anatomical and physiological measurements to create “bottom-up” receptive field models that have predictive power. 2) Models that explore the distribution of information across cell types and the dynamics of the representation of visual information. The rich content of the visual world in encoded in ~20 parallel ganglion cell channels. What rules govern how visual information is distributed among these channels? How do these rules depend on the statistics of the visual scene?
Intravitreal Injections
Intravitreal injections involve the delivery of substances, such as viruses or other compounds, directly into the vitreous cavity of the eye. This technique is particularly useful for studying the visual system, as it allows researchers to identify and trace neurons from the retina to the brain. By using viruses with fluorescent properties, researchers can track the axonal projections of retinal ganglion cells (RGCs), providing insights into the organization and connectivity of the visual pathway.
Intracerebral Stereotaxic Injections
Stereotaxic injections offer a highly flexible and precise method for delivering substances into specific brain regions. This technique involves the use of a stereotaxic apparatus to guide the injection needle to the desired coordinates within the brain. Researchers can adjust various parameters, such as the concentration of the injected substance, the age of the animal, and the targeted brain area, depending on the specific research question being addressed. Additionally, stereotaxic injections can be performed in a wide range of animal species, allowing for comparative studies and the translation of findings to human health.
Single Cell Transcriptomics
In our lab, we leverage single-cell transcriptomics to unravel the diversity and function of retinal neurons, particularly retinal ganglion cells (RGCs). Using single-cell transcriptomics, we’ve uncovered rare RGC subtypes, identified reliable genetic markers, and clarified how different cell types contribute to visual processing. This molecular insight enhances our ability to dissect retinal circuits and opens up new avenues for targeted therapeutic strategies. Our goal is to create a unified classification system that links gene expression with neuronal function and morphology.
Mouse Psychophysics
In our lab, we combine circuit-level neuroscience with mouse psychophysics to understand how the retina transforms visual input into perception. We begin by characterizing distinct retinal ganglion cell types through their physiological responses and morphology, linking them to specific roles in visual processing. To test how these neural signals contribute to perception, we train head-fixed mice on visual discrimination tasks using two-alternative forced choice paradigms. These tasks allow us to precisely measure perceptual thresholds for features like contrast, motion, and dynamic patterns. By manipulating specific retinal circuits using optogenetics or chemogenetics during behavior, we can causally link defined cell types to specific perceptual outcomes. This integrative approach allows us to trace visual computations from neural circuits to behavior, bridging the gap between the retina and the brain's interpretation of the visual world.
Ocular Perfusion
We also employ ocular perfusion techniques to investigate retinal function under physiologically relevant conditions. This includes both in vivo eye perfusion approaches and our lab’s development of an isolated perfused eye model. In our preparation, we maintain the retina’s neurovascular environment ex vivo by perfusing an enucleated mouse eye with oxygenated, nutrient-rich media while preserving intraocular pressure and vascular access. This setup allows us to deliver drugs, manipulate glucose or oxygen levels, and record retinal ganglion cell activity over extended periods—all without disrupting the eye’s structural integrity. By combining precise control of the retinal microenvironment with high-resolution physiological recordings, we’re able to explore how vascular, metabolic, and neural factors interact in real time. This platform is particularly powerful for studying diseases like diabetic retinopathy, where metabolic stress plays a critical role, and for screening therapeutic interventions that rely on intact retinal vasculature.
Immunohistochemistry
We use immunohistochemistry to visualize and quantify protein expression across defined retinal cell types and circuits. By applying fluorescently labeled antibodies to fixed tissue, we can localize markers of interest—ranging from synaptic proteins and neurotransmitter receptors to disease-related targets and cellular stress indicators. This technique allows us to validate molecular identities, assess structural changes, and map the spatial distribution of key proteins within the retina. In many cases, we combine immunostaining with genetic labeling or electrophysiological characterization to correlate molecular profiles with functional outcomes. Whether confirming cell-type specificity, monitoring disease progression, or evaluating the effects of experimental manipulations, immunohistochemistry remains a foundational tool in how we link molecular expression to circuit structure and function.