scholarly journals Deep brain fluorescence imaging with minimally invasive ultra-thin optical fibers

2017 ◽  
Author(s):  
Shay Ohayon ◽  
Antonio M. Caravaca-Aguirre ◽  
Rafael Piestun ◽  
James J. DiCarlo
Keyword(s):  
Optical Fibers ◽  
Neural Activity ◽  
Brain Regions ◽  
Volumetric Imaging ◽  
Non Invasive ◽  
Cellular Resolution ◽  
Calcium Indicator ◽  
Acquisition Speed ◽  
Resolution Imaging

AbstractA major open challenge in neuroscience is the ability to measure and perturb neural activity in vivo from well-defined neural sub-populations at cellular resolution anywhere in the brain. However, limitations posed by scattering and absorption prohibit non-invasive (surface) multiphoton approaches1,2 for deep (>2mm) structures, while Gradient Refreactive Index (GRIN) endoscopes2–4 are thick and cause significant damage upon insertion. Here, we demonstrate a novel microendoscope to image neural activity at arbitrary depths via an ultrathin multimode optical fiber (MMF) probe that is 5-10X thinner than commercially available microendoscopes. We demonstrate micron-scale resolution, multispectral and volumetric imaging. In contrast to previous approaches1,5–8 we show that this method has an improved acquisition speed that is sufficient to capture rapid neuronal dynamics in-vivo in rodents expressing a genetically encoded calcium indicator. Our results emphasize the potential of this technology in neuroscience applications and open up possibilities for cellular resolution imaging in previously unreachable brain regions.

scholarly journals Large-scale cellular-resolution imaging of neural activity in freely behaving mice

2021 ◽  
Author(s):  
D.P. Leman ◽  
I.A. Chen ◽  
K.A. Bolding ◽  
J. Tai ◽  
L.K. Wilmerding ◽  
...  
Keyword(s):  
Neural Activity ◽  
Large Scale ◽  
First Generation ◽  
Brain Regions ◽  
Field Of View ◽  
Cellular Resolution ◽  
Neural Populations ◽  
Resolution Imaging ◽  
Freely Behaving ◽  
Freely Moving

AbstractMiniaturized microscopes for head-mounted fluorescence imaging are powerful tools for visualizing neural activity during naturalistic behaviors, but the restricted field of view of first-generation ‘miniscopes’ limits the size of neural populations accessible for imaging. Here we describe a novel miniaturized mesoscope offering cellular-resolution imaging over areas spanning several millimeters in freely moving mice. This system enables comprehensive visualization of activity across entire brain regions or interactions across areas.

scholarly journals Imaging Subthreshold Voltage Oscillation With Cellular Resolution in the Inferior Olive in vitro

2020 ◽  
Vol 14 ◽  
Author(s):  
Kevin Dorgans ◽  
Bernd Kuhn ◽  
Marylka Yoe Uusisaari
Keyword(s):  
Inferior Olive ◽  
Brain Slices ◽  
Brain Regions ◽  
Mammalian Brain ◽  
Wide Field ◽  
Voltage Imaging ◽  
Subthreshold Oscillations ◽  
Cellular Resolution

Voltage imaging with cellular resolution in mammalian brain slices is still a challenging task. Here, we describe and validate a method for delivery of the voltage-sensitive dye ANNINE-6plus (A6+) into tissue for voltage imaging that results in higher signal-to-noise ratio (SNR) than conventional bath application methods. The not fully dissolved dye was injected into the inferior olive (IO) 0, 1, or 7 days prior to acute slice preparation using stereotactic surgery. We find that the voltage imaging improves after an extended incubation period in vivo in terms of labeled volume, homogeneous neuropil labeling with saliently labeled somata, and SNR. Preparing acute slices 7 days after the dye injection, the SNR is high enough to allow single-trial recording of IO subthreshold oscillations using wide-field (network-level) as well as high-magnification (single-cell level) voltage imaging with a CMOS camera. This method is easily adaptable to other brain regions where genetically-encoded voltage sensors are prohibitively difficult to use and where an ultrafast, pure electrochromic sensor, like A6+, is required. Due to the long-lasting staining demonstrated here, the method can be combined, for example, with deep-brain imaging using implantable GRIN lenses.

scholarly journals Targeted Molecular Imaging Using Aptamers in Cancer

2018 ◽  
Vol 11 (3) ◽  
pp. 71 ◽  
Author(s):  
Sorah Yoon ◽  
John Rossi
Keyword(s):  
Wide Spectrum ◽  
Rna Aptamers ◽  
Tissue Imaging ◽  
Live Cells ◽  
Target Cells ◽  
New Class ◽  
Non Invasive ◽  
Resolution Imaging ◽  
Tissue Specimens

Imaging is not only seeing, but also believing. For targeted imaging modalities, nucleic acid aptamers have features such as superior recognition of structural epitopes and quick uptake in target cells. This explains the emergence of an evolved new class of aptamers into a wide spectrum of imaging applications over the last decade. Genetically encoded biosensors tagged with fluorescent RNA aptamers have been developed as intracellular imaging tools to understand cellular signaling and physiology in live cells. Cancer-specific aptamers labeled with fluorescence have been used for assessment of clinical tissue specimens. Aptamers conjugated with gold nanoparticles have been employed to develop innovative mass spectrometry tissue imaging. Also, use of chemically conjugated cancer-specific aptamers as probes for non-invasive and high-resolution imaging has been transformative for in vivo imaging in multiple cancers.

scholarly journals Modal demultiplexing properties of tapered and nanostructured optical fibers for in vivo optogenetic control of neural activity

2015 ◽  
Vol 6 (10) ◽  
pp. 4014 ◽  
Author(s):  
Marco Pisanello ◽  
Andrea Della Patria ◽  
Leonardo Sileo ◽  
Bernardo L. Sabatini ◽  
Massimo De Vittorio ◽  
...  
Keyword(s):  
Optical Fibers ◽  
Neural Activity ◽  
Optogenetic Control

scholarly journals Dual-color volumetric imaging of neural activity of cortical columns

2018 ◽  
Author(s):  
Shuting Han ◽  
Weijian Yang ◽  
Rafael Yuste
Keyword(s):  
Neural Activity ◽  
High Speed ◽  
Neural Circuits ◽  
Emergent Properties ◽  
Spatiotemporal Resolution ◽  
Population Activity ◽  
Volumetric Imaging ◽  
Two Photon ◽  
Dual Color

To capture the emergent properties of neural circuits, high-speed volumetric imaging of neural activity at cellular resolution is desirable. But while conventional two-photon calcium imaging is a powerful tool to study population activity in vivo, it is restrained to two-dimensional planes. Expanding it to 3D while maintaining high spatiotemporal resolution appears necessary. Here, we developed a two-photon microscope with dual-color laser excitation that can image neural activity in a 3D volume. We imaged the neuronal activity of primary visual cortex from awake mice, spanning from L2 to L5 with 10 planes, at a rate of 10 vol/sec, and demonstrated volumetric imaging of L1 long-range PFC projections and L2/3 somatas. Using this method, we map visually-evoked neuronal ensembles in 3D, finding a lack of columnar structure in orientation responses and revealing functional correlations between cortical layers which differ from trial to trial and are missed in sequential imaging. We also reveal functional interactions between presynaptic L1 axons and postsynaptic L2/3 neurons. Volumetric two-photon imaging appears an ideal method for functional connectomics of neural circuits.

scholarly journals Cellular resolution imaging of vestibular processing across the larval zebrafish brain

2018 ◽  
Author(s):  
Itia A. Favre-Bulle ◽  
Gilles Vanwalleghem ◽  
Michael A. Taylor ◽  
Halina Rubinsztein-Dunlop ◽  
Ethan K. Scott
Keyword(s):  
Vestibular System ◽  
Cellular Responses ◽  
Vestibular Stimulation ◽  
Brain Regions ◽  
Larval Zebrafish ◽  
Cellular Resolution ◽  
Separate Control ◽  
Resolution Imaging ◽  
Apply Physical ◽  
The Brain

SummaryThe vestibular system, which reports on motion and gravity, is essential to postural control, balance, and egocentric representations of movement and space. The motion needed to stimulate the vestibular system complicates studying its circuitry, so we previously developed a method for fictive vestibular stimulation in zebrafish, using optical trapping to apply physical forces to the otoliths. Here, we combine this fictive stimulation with whole-brain calcium imaging at cellular resolution, delivering a comprehensive map of the brain regions and cellular responses involved in basic vestibular processing. We find these responses to be broadly distributed across the brain, with unique profiles of cellular responses and topography in each brain region. The most widespread and abundant responses involve excitation that is rate coded to the stimulus strength. Other responses, localized to the telencephalon and habenulae, show excitation that is only weakly rate coded and that is sensitive to weak stimuli. Finally, numerous brain regions contain neurons that are inhibited by vestibular stimuli, and these inhibited neurons are often tightly localised spatially within their regions. By exerting separate control over the left and right otoliths, we explore the laterality of brain-wide vestibular processing, distinguishing between neurons with unilateral and bilateral vestibular sensitivity, and revealing patterns by which conflicting vestibular signals from the two ears can be mutually cancelling. Our results show a broader and more extensive network of vestibular responsive neurons than has previously been described in larval zebrafish, and provides a framework for more targeted studies of the underlying functional circuits.

scholarly journals A protein-based biosensor for detecting calcium by magnetic resonance imaging

2021 ◽  
Author(s):  
Harun F. Ozbakir ◽  
Austin D.C. Miller ◽  
Kiara B. Fishman ◽  
André F. Martins ◽  
Tod E. Kippin ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Neural Activity ◽  
Calcium Binding ◽  
Relaxation Times ◽  
Neuronal Cell ◽  
Brain Regions ◽  
Resonance Imaging ◽  
Biologically Relevant

ABSTRACTCalcium-responsive contrast agents for magnetic resonance imaging (MRI) offer an attractive approach to noninvasively image neural activity with wide coverage in deep brain regions. However, current MRI sensors for calcium are based on synthetic architectures fundamentally incompatible with genetic technologies for in vivo delivery and targeting. Here, we present a protein-based MRI sensor for calcium, derived from a calcium-binding protein known as calprotectin. Calcium-binding causes calprotectin to sequester manganese. We demonstrate that this mechanism allows calprotectin to alter T1 and T2 weighted contrast in response to biologically relevant calcium concentrations. Corresponding changes in relaxation times are comparable to synthetic calcium sensors and exceed those of previous protein-based MRI sensors for other neurochemical targets. The biological applicability of calprotectin was established by detecting calcium in lysates prepared from a neuronal cell line. Calprotectin thus represents a promising path towards imaging neural activity by combining the benefits of MRI and protein sensors.

scholarly journals All-optical imaging and patterned stimulation with a one-photon endoscope

2021 ◽  
Author(s):  
Jinyong Zhang ◽  
Ryan N Hughes ◽  
Namsoo Kim ◽  
Isabella P Fallon ◽  
Konstantin I bakhurin ◽  
...  
Keyword(s):  
Neural Activity ◽  
Calcium Imaging ◽  
Neural Circuit ◽  
Integrated System ◽  
Striatal Neurons ◽  
Indirect Pathway ◽  
Cellular Resolution ◽  
All Optical ◽  
Freely Moving

While in vivo calcium imaging makes it possible to record activity in defined neuronal populations with cellular resolution, optogenetics allows selective manipulation of neural activity. Recently, these two tools have been combined to stimulate and record neural activity at the same time, but current approaches often rely on two-photon microscopes that are difficult to use in freely moving animals. To address these limitations, we have developed a new integrated system combining a one-photon endoscope and a digital micromirror device for simultaneous calcium imaging and precise optogenetic photo-stimulation with near cellular resolution (Miniscope with All-optical Patterned Stimulation and Imaging, MAPSI). Using this highly portable system in freely moving mice, we were able to image striatal neurons from either the direct pathway or the indirect pathway while simultaneously activating any neuron of choice in the field of view, or to synthesize arbitrary spatiotemporal patterns of photo-stimulation. We could also select neurons based on their relationship with behavior and recreate the behavior by mimicking the natural neural activity with photo-stimulation. MAPSI thus provides a powerful tool for interrogation of neural circuit function in freely moving animals.

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