- Neuroscience and Neuropharmacology Research
- Advanced Fluorescence Microscopy Techniques
- Photoreceptor and optogenetics research
- Neural dynamics and brain function
- Memory and Neural Mechanisms
- Neuroscience and Neural Engineering
- Photoacoustic and Ultrasonic Imaging
- Optical Coherence Tomography Applications
- Cell Image Analysis Techniques
- Single-cell and spatial transcriptomics
- Advanced Memory and Neural Computing
- Advanced Chemical Sensor Technologies
- Neuroinflammation and Neurodegeneration Mechanisms
- Zebrafish Biomedical Research Applications
- Ion channel regulation and function
- Nicotinic Acetylcholine Receptors Study
- Spectroscopy Techniques in Biomedical and Chemical Research
- Sleep and Wakefulness Research
- Molecular Sensors and Ion Detection
- Optical Polarization and Ellipsometry
- Gene Regulatory Network Analysis
- Neurobiology and Insect Physiology Research
Columbia University
2021-2025
Allen Institute
2024-2025
Allen Institute for Neural Dynamics
2024-2025
Vrije Universiteit Amsterdam
2010-2022
Amsterdam Neuroscience
2010-2022
New York Proton Center
2021
Brain (Germany)
2021
Laboratoire d’immunologie intégrative du cancer
2017
Dendritic calcium signaling is central to neural plasticity mechanisms that allow animals adapt the environment. Intracellular release (ICR) from endoplasmic reticulum has long been thought shape these mechanisms. However, ICR not investigated in mammalian neurons vivo. We combined electroporation of single CA1 pyramidal neurons, simultaneous imaging dendritic and somatic activity during spatial navigation, optogenetic place field induction, acute genetic augmentation cytosolic impact reveal...
The ability to visualize neurons inside living brain tissue is a fundamental requirement in neuroscience and neurosurgery. Especially the development of noninvasive probe morphology with micrometer-scale resolution highly desirable, as it would provide approach optical biopsies diagnostic medicine. Two-photon laser-scanning microscopy (2PLSM) powerful tool this regard, has become standard for minimally invasive high-resolution imaging biological samples. However, while 2PLSM-based methods...
Optical recording of membrane potential permits spatially resolved measurement electrical activity in subcellular regions single cells, which would be inaccessible to electrodes, and imaging spatiotemporal patterns action propagation excitable tissues, such as the brain or heart. However, available voltage-sensitive dyes (VSDs) are not always spectrally compatible with newly optical technologies for sensing manipulating physiological state a system. Here, we describe series 19 fluorinated...
Abstract Learning and memory are fundamental to adaptive behavior cognition. Various forms of synaptic plasticity have been proposed as cellular substrates for the emergence feature selectivity in neurons underlying episodic memory. However, despite decades work, our understanding how underlies encoding remains limited, largely due a shortage tools technical challenges associated with visualization at single-neuron resolution awake-behaving animals. Behavioral Timescale Synaptic Plasticity...
In laser-scanning microscopy often an off-the-shelf achromatic doublet is used as a scan lens which can reduce the available diffraction-limited field-of-view (FOV) by factor of 3 and introduce chromatic aberrations that are angle dependent. Here we present several simple designs superior quality fully make use high-NA low-magnification objectives, offering imaging over large FOV wavelength range. We constructed two-photon microscope with optimized custom lenses had near diffraction limit...
Abstract Identifying the input-output operations of neurons requires measurements synaptic transmission simultaneously at many a neuron’s thousands inputs in intact brain. To facilitate this goal, we engineered and screened 3365 variants fluorescent protein glutamate indicator iGluSnFR3 neuron culture, selected mouse visual cortex. Two have high sensitivity, fast activation (< 2 ms) deactivation times tailored for recording large populations synapses (iGluSnFR4s, 153 or rapid dynamics...
<title>Abstract</title> Identifying the input-output operations of neurons requires measurements synaptic transmission simultaneously at many a neuron’s thousands inputs in intact brain. To facilitate this goal, we engineered and screened 3365 variants fluorescent protein glutamate indicator iGluSnFR3 neuron culture, selected mouse visual cortex. Two have high sensitivity, fast activation (< 2 ms) deactivation times tailored for recording large populations synapses (iGluSnFR4s, 153 or...
Optical clearing methods serve as powerful tools to study intact organs and neuronal circuits. We developed an aqueous protocol, Fast 3D Clear, that relies on tetrahydrofuran for tissue delipidation iohexol clearing, such tissues can be imaged under immersion oil in light-sheet imaging systems. Clear requires 3 days achieve high transparency of adult embryonic mouse while maintaining their anatomical integrity preserving a vast array transgenic viral/dye fluorophores. A unique advantage is...
Fast electrical signaling in dendrites is central to neural computations that support adaptive behaviors. Conventional techniques lack temporal and spatial resolution the ability track underlying membrane potential dynamics present across complex three-dimensional dendritic arbor vivo. Here, we perform fast two-photon imaging of somatic single pyramidal cells CA1 region mouse hippocampus during awake behavior. We study subthreshold suprathreshold events throughout vivo by combining voltage...
Abstract Neuronal spiking activity is routinely recorded using genetically encoded calcium indicators (GECIs), but imaging limited in temporal resolution and does not report subthreshold voltage changes. Genetically (GEVIs) offer better sensitivity, spike detection with fast GEVIs has required specialized equipment. Here, we the ASAP4 subfamily of that brighten response to membrane depolarization, inverting fluorescence-voltage relationship previous ASAP GEVIs. Two variants, ASAP4b ASAP4e,...
Synaptic inputs that target distal regions of neuronal dendrites can often generate local dendritic spikes amplify synaptic depolarization, induce plasticity, and enhance output. However, are subject to significant attenuation by cable properties, produce only a weak subthreshold depolarization the soma. Nonetheless, such have been implicated in memory storage, sensory perception place field formation. How somatic response powerful behavioral effects? Here, we use dual recordings acute...
Summary Astrocyte distal processes, known as leaflets or perisynaptic astrocyte processes (PAPs), fine-tune synaptic activity by clearing neurotransmitters and limiting extrasynaptic glutamate diffusion. While learning memory depends on orchestrated of neuronal ensembles within the hippocampus, it is becoming increasingly evident that astrocytes residing in environment these synapses play a central role shaping memories. However, how astroglial coverage contributes to mnemonic processing...
Fast electrical signaling in dendrites is central to neural computations that support adaptive behaviors. Conventional techniques lack temporal and spatial resolution the ability track underlying membrane potential dynamics present across complex three-dimensional dendritic arbor vivo . Here, we perform fast two-photon imaging of somatic single pyramidal cells CA1 region mouse hippocampus during awake behavior. We study subthreshold suprathreshold events throughout by combining voltage with...
We demonstrate that optical third-harmonic generation (THG) microscopy enables high-resolution live brain imaging without the need for external contrast agents. find specific geometry and lipid content of tissue leads to partial phase-matching THG outside neuronal cell bodies, producing high-contrast shadow images in which neurons are clearly visible.
We demonstrate high-resolution live brain tissue imaging without fluorescent dyes, using third-harmonic generation. Targeted patching of living neurons is demonstrated, and label-free images fixed human have been obtained.