A5064901405- Photoreceptor and optogenetics research
- Neural dynamics and brain function
- Neuroscience and Neural Engineering
- Optical Imaging and Spectroscopy Techniques
- Advanced Fluorescence Microscopy Techniques
- Phosphodiesterase function and regulation
- Nitric Oxide and Endothelin Effects
- Photoacoustic and Ultrasonic Imaging
- Receptor Mechanisms and Signaling
- Neuroscience and Neuropharmacology Research
- Advanced MRI Techniques and Applications
- Functional Brain Connectivity Studies
- Traumatic Brain Injury and Neurovascular Disturbances
- Cell Image Analysis Techniques
- Advanced biosensing and bioanalysis techniques
- EEG and Brain-Computer Interfaces
- Optical Coherence Tomography Applications
- Conducting polymers and applications
- Analytical Chemistry and Sensors
- 3D Printing in Biomedical Research
- Reproductive Biology and Fertility
- RNA and protein synthesis mechanisms
- Crystal structures of chemical compounds
- Neurological Disease Mechanisms and Treatments
- RNA Interference and Gene Delivery
Boston University
2021-2025
Massachusetts General Hospital
2021
University of California, San Diego
2016-2020
University of Tübingen
2012-2018
University of Lübeck
2013
Siemens (Germany)
2011
University of Münster
1984
Czech Academy of Sciences, Institute of Inorganic Chemistry
1983
Identification of the cellular players and molecular messengers that communicate neuronal activity to vasculature driving cerebral hemodynamics is important for (1) basic understanding cerebrovascular regulation (2) interpretation functional Magnetic Resonance Imaging (fMRI) signals. Using a combination optogenetic stimulation 2-photon imaging in mice, we demonstrate selective activation cortical excitation inhibition elicits distinct vascular responses identify vasoconstrictive mechanism as...
Abstract Recent advances in optical technologies such as multi-photon microscopy and optogenetics have revolutionized our ability to record manipulate neuronal activity. Combining techniques with electrical recordings is of critical importance connect the large body neuroscience knowledge obtained from animal models human studies mainly relying on electrophysiological brain-scale However, integration modalities challenging due generation light-induced artifacts. Here we report a transparent...
Significance By imaging cyclic GMP (cGMP) in live ovarian follicles from mice, we show how luteinizing hormone signaling the follicle periphery results a rapid decrease cGMP oocyte, thus reinitiating meiosis. Luteinizing lowers outer cells of follicle, then oocyte decreases as consequence diffusion through gap junctions. These findings demonstrate directly that physiological signal initiated by stimulus one region an intact tissue can travel across many layers via nucleotide
Human cortical organoids, three-dimensional neuronal cultures, are emerging as powerful tools to study brain development and dysfunction. However, whether organoids can functionally connect a sensory network in vivo has yet be demonstrated. Here, we combine transparent microelectrode arrays two-photon imaging for longitudinal, multimodal monitoring of human transplanted into the retrosplenial cortex adult mice. Two-photon shows vascularization organoid. Visual stimuli evoke...
To explore the functional significance of cGMP-dependent protein kinase type I (cGKI) in regulation erythrocyte survival, gene-targeted mice lacking cGKI were compared with their control littermates. By age 10 weeks, cGKI-deficient exhibited pronounced anemia and splenomegaly. Compared mice, mutants had significantly lower red blood cell count, packed volume, hemoglobin concentration. Anemia was associated a higher reticulocyte number an increase plasma erythropoietin The spleens mutant...
Cyclic GMP (cGMP) is an important intracellular signaling molecule in the cardiovascular system, but its spatiotemporal dynamics vivo largely unknown.To generate and characterize transgenic mice expressing fluorescence resonance energy transfer-based ratiometric cGMP sensor, indicator with EC50 of 500 nmol/L (cGi500), tissues.Mouse lines smooth muscle-specific or ubiquitous expression cGi500 were generated by random transgenesis using SM22α promoter fragment targeted integration a Cre...
The enhanced electrochemical activity of nanostructured materials is readily exploited in energy devices, but their utility scalable and human-compatible implantable neural interfaces can significantly advance the performance clinical research electrodes. We utilize low-temperature selective dealloying to develop biocompatible one-dimensional platinum nanorod (PtNR) arrays that exhibit superb properties at various length scales, stability, biocompatibility for high neurotechnologies. PtNR...
Sildenafil, an inhibitor of the cGMP-degrading phosphodiesterase 5 that is used to treat erectile dysfunction, has been linked increased risk melanoma. Here, we have examined potential connection between cGMP-dependent signaling cascades and melanoma growth. Using a combination biochemical assays real-time monitoring cells, report growth-promoting pathway in murine human cells. We document C-type natriuretic peptide (CNP), ligand membrane-bound guanylate cyclase B, enhances activity protein...
Abstract The Utah array powers cutting‐edge projects for restoration of neurological function, such as BrainGate, but the underlying electrode technology has itself advanced little in last three decades. Here, dual‐side lithographic microfabrication processes is exploited to demonstrate a 1024‐channel penetrating silicon microneedle (SiMNA) that scalable its recording capabilities and cortical coverage suitable clinical translation. SiMNA first with flexible backing affords compliancy brain...
Neurophotonics was launched in 2014 coinciding with the launch of BRAIN Initiative focused on development technologies for advancement neuroscience. For last seven years, Neurophotonics' agenda has been well aligned this focus neurotechnologies featuring new optical methods and tools applicable to brain studies. While 2.0 is pivoting towards applications these novel quest understand brain, article we review an extensive diverse toolkit explore function that have emerged from related...
Despite the importance of understanding regulation microvascular blood flow in white matter, no data on subcortical capillary parameters are available, largely due to lack appropriate imaging methods. To address this knowledge gap, we employed two-photon microscopy using a far-red fluorophore Alexa680 and photon-counting detection measure red cell (RBC) flux both cerebral gray isoflurane-anesthetized mice. We have found that control animals, baseline RBC matter was significantly higher than...
Optical methods that rely on fluorescence for mapping changes in neuronal membrane potential the brains of awake animals provide a powerful way to interrogate activity neurons underlie neural computations ranging from sensation and perception learning memory. To achieve this goal, fluorescent indicators should be bright, highly sensitive small potential, nontoxic, excitable with infrared light. We report new class fluorescent, voltage-sensitive dyes: sulfonated rhodamine voltage reporters...
Poly(3,4-ethylenenedioxythiophene) or PEDOT is a promising candidate for next-generation neuronal electrode materials but its weak adhesion to underlying metallic conductors impedes potential. An effective method of mechanically anchoring the within an Au nanorod (Au-nr) structure reported and it demonstrated that provides enhanced overall layer stability. Cyclic voltammetry (CV) stress used investigate stability spin-cast electrodeposited PEDOT. The Au-nr permits 10 000 CV cycles coated...
Chronic cranial windows allow for longitudinal brain imaging experiments in awake, behaving mice. Different technologies have their unique advantages and combining multiple modalities offers measurements of a wide spectrum neuronal, glial, vascular, metabolic parameters needed comprehensive investigation physiological pathophysiological mechanisms. Here, we detail suite surgical techniques installation different targeted specific combination. Following these practices will yield higher...
Abstract Neurovascular coupling (NVC) modulates cerebral blood flow to match increased metabolic demand during neuronal excitation. Activation of inhibitory interneurons also increase flow, but the basis for NVC caused by is unclear. While astrocyte Ca 2+ levels rise with excitatory neural transmission, much less known regards astrocytic sensitivity neurotransmission. We performed two‐photon microscopy in awake mice examine correlation between and NVC, evoked activation either all (VGAT IN )...
Inducing apparent memory recall by tagging and optogenetically reactivating cells in the hippocampus was demonstrated over a decade ago. However, hippocampal dynamics resulting from this reactivation remain largely unknown. While calcium imaging is commonly used as measure of neuronal activity, GCaMP, most common indicator, cannot be with optogenetic because both require blue light excitation. To resolve overlap, we demonstrate red-shifted opsin, ChrimsonR. We then conduct dual-color CA1...
Abstract Many pathophysiological processes are associated with proliferation, migration or death of distinct cell populations. Monitoring specific types and their progeny in a non-invasive, longitudinal quantitative manner is still challenging. Here we show novel cell-tracking system that combines Cre/lox-assisted fate mapping thymidine kinase (sr39tk) reporter gene for detection by positron emission tomography (PET). We generate Rosa26-mT/sr39tk PET mice induce sr39tk expression platelets,...
Mechanisms that limit thrombosis are poorly defined. One of the few known endogenous platelet inhibitors is nitric oxide (NO). NO activates sensitive guanylyl cyclase (NO-GC) in platelets, resulting an increase cyclic guanosine monophosphate (cGMP). Here we show, using cGMP sensor mice to study spatiotemporal dynamics cGMP, NO-induced production pre-activated platelets strongly shear-dependent. We delineate a new mode platelet-inhibitory mechanotransduction via shear-activated NO-GC followed...
Electrocorticography (ECoG) is becoming more prevalent due to improvements in fabrication and recording technology as well its ease of implantation compared intracortical electrophysiology, larger cortical coverage, potential advantages for use long term chronic implantation. Given the flexibility design ECoG grids, which only increasing, it remains an open question what geometry electrodes optimal application. Conductive polymer, PEDOT:PSS, coated microelectrodes have advantage that they...
The cerebral cortex is organized in cortical layers that differ their cellular density, composition, and wiring. Cortical laminar architecture also readily revealed by staining for cytochrome oxidase—the last enzyme the respiratory electron transport chain located inner mitochondrial membrane. It has been hypothesized a high-density band of oxidase layer IV reflects higher oxygen consumption under baseline (unstimulated) conditions. Here, we tested above hypothesis using direct measurements...
The increasing use of genetically engineered mice as animal models human disease in biomedical research, latest advances imaging technologies, and development novel, highly specific radiolabeled biomarkers provide great potential to study receptor expression gene function vivo mice. (11)C-raclopride is a widely used PET tracer measure striatal D(2) binding was test the feasibility multiple-ligand-concentration assay for quantification.Mice underwent total 4 scans with decreasing activities...