NINscope, a versatile miniscope for multi-region circuit investigations

Groot, Andres de; Boom, Bastijn J.G. van den; Genderen, Romano M van; Coppens, Joris E.; Veldhuijzen, John van; Bos, Joop; Hoedemaker, Hugo; Negrello, Mario; Willuhn, Ingo; Zeeuw, Chris I. De; Hoogland, Tycho M.

doi:10.7554/elife.49987

Cited by 123 publications

(87 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The design takes advantage of the sensors made available through the open source miniature imaging systems pipeline 27 . This is a rapidly evolving ecosystem where new sensors with increased sensitivity and imaging speed 52 , miniaturization 53 , wireless imaging capabilities 54 being developed. Relatively simple modifications to the current Mesoscope design will allow these newer sensors to be incorporated.…”

Section: Discussionmentioning

confidence: 99%

Miniaturized head-mounted device for whole cortex mesoscale imaging in freely behaving mice

Rynes

Surinach

Linn

et al. 2020

Preprint

View full text Add to dashboard Cite

The advent of genetically encoded calcium indicators, along with surgical preparations such as thinned skulls or refractive index matched skulls, have enabled mesoscale cortical activity imaging in head-fixed mice. Such imaging studies have revealed complex patterns of coordinated activity across the cortex during spontaneous behaviors, goal-directed behavior, locomotion, motor learning, and perceptual decision making. However, neural activity during unrestrained behavior significantly differs from neural activity in head-fixed animals. Whole-cortex imaging in freely behaving mice will enable the study of neural activity in a larger, more complex repertoire of behaviors not possible in head-fixed animals. Here we present the “Mesoscope,” a wide-field miniaturized, head-mounted fluorescence microscope compatible with transparent polymer skulls recently developed by our group. With a field of view of 8 mm x 10 mm and weighing less than 4 g, the Mesoscope can image most of the mouse dorsal cortex with resolution ranging from 39 to 56 µm. Stroboscopic illumination with blue and green LEDs allows for the measurement of both fluorescence changes due to calcium activity and reflectance signals to capture hemodynamic changes. We have used the Mesoscope to successfully record mesoscale calcium activity across the dorsal cortex during sensory-evoked stimuli, open field behaviors, and social interactions. Finally, combining the mesoscale imaging with electrophysiology enabled us to measure dynamics in extracellular glutamate release in the cortex during the transition from wakefulness to natural sleep.

show abstract

Section: Discussionmentioning

confidence: 99%

Miniaturized head-mounted device for whole cortex mesoscale imaging in freely behaving mice

Rynes

Surinach

Linn

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…While these initial projects improved the functionality of the epifluorescent miniscope, other designs chose to maximize the amount of data collected during experiments. For example, the NINscope [8] further miniaturized the mechanical design to allow the simultaneous recording of two brain regions using two scopes on a single mouse. The cScope [9] instead employed a bulkier and more optically complex design to provide a mm-scale Field of View (FOV) for widefield imaging of the neocortex of rat.…”

Section: Introductionmentioning

confidence: 99%

Design of a high-resolution light field miniscope for volumetric imaging in scattering tissue

Chen¹,

Xiong²,

Xue³

et al. 2020

Biomed. Opt. Express

View full text Add to dashboard Cite

Integrating light field microscopy techniques with existing miniscope architectures has allowed for volumetric imaging of targeted brain regions in freely moving animals. However, the current design of light field miniscopes is limited by non-uniform resolution and long imaging path length. In an effort to overcome these limitations, this paper proposes an optimized Galilean-mode light field miniscope (Gali-MiniLFM), which achieves a more consistent resolution and a significantly shorter imaging path than its conventional counterparts. In addition, this paper provides a novel framework that incorporates the anticipated aberrations of the proposed Gali-MiniLFM into the point spread function (PSF) modeling. This more accurate PSF model can then be used in 3D reconstruction algorithms to further improve the resolution of the platform. Volumetric imaging in the brain necessitates the consideration of the effects of scattering. We conduct Monte Carlo simulations to demonstrate the robustness of the proposed Gali-MiniLFM for volumetric imaging in scattering tissue.

show abstract

“…Despite the broad success of GECIs in in vivo imaging, tracking neural activity with behavior is limited due to the necessity to head-fix organisms to obtain high-resolution images (Tian et al, 2009;Sun et al, 2013) except for the development of the miniscope for rodents and other small mammals (Aharoni and Hoogland, 2019). However, the field of view is often limited by the necessity to deliver light into the brain and may require a priori knowledge of the specific brain region relevant to the specific stimulus, regardless of whether the animal is head-fixed under a microscope or freely-moving with a miniscope (Aharoni and Hoogland, 2019;de Groot et al, 2020). Because some circuit activity is so short-lived, it may escape detection unless the experimenter has specific knowledge of where and when to image.…”

Section: Introductionmentioning

confidence: 99%

The Photoconvertible Fluorescent Probe, CaMPARI, Labels Active Neurons in Freely-Moving Intact Adult Fruit Flies

Edwards

Hoppa

Bosco

2020

Front. Neural Circuits

View full text Add to dashboard Cite

Linking neural circuitry to behavior by mapping active neurons in vivo is a challenge. Both genetically encoded calcium indicators (GECIs) and intermediate early genes (IEGs) have been used to pinpoint active neurons during a stimulus or behavior but have drawbacks such as limiting the movement of the organism, requiring a priori knowledge of the active region or having poor temporal resolution. Calcium-modulated photoactivatable ratiometric integrator (CaMPARI) was engineered to overcome these spatial-temporal challenges. CaMPARI is a photoconvertible protein that only converts from green to red fluorescence in the presence of high calcium concentration and 405 nm light. This allows the experimenter to precisely mark active neurons within defined temporal windows. The photoconversion can then be quantified by taking the ratio of the red fluorescence to the green. CaMPARI promises the ability to trace active neurons during a specific stimulus; however, CaMPARI's uses in adult Drosophila have been limited to photoconversion during fly immobilization. Here, we demonstrate a method that allows photoconversion of multiple freely-moving intact adult flies during a stimulus. Flies were placed in a dish with filter paper wet with acetic acid (pH = 2) or neutralized acetic acid (pH = 7) and exposed to photoconvertible light (60 mW) for 30 min (500 ms on, 200 ms off). Immediately following photoconversion, whole flies were fixed and imaged by confocal microscopy. The red:green ratio was quantified for the DC4 glomerulus, a bundle of neurons expressing Ir64a, an ionotropic receptor that senses acids in the Drosophila antennal lobe. Flies exposed to acetic acid showed 1.3-fold greater photoconversion than flies exposed to neutralized acetic acid. This finding was recapitulated using a more physiological stimulus of apple cider vinegar. These results indicate that CaMPARI can be used to label neurons in intact, freely-moving adult flies and will be useful for identifying the circuitry underlying complex behaviors.

show abstract

NINscope, a versatile miniscope for multi-region circuit investigations

Cited by 123 publications

References 62 publications

Miniaturized head-mounted device for whole cortex mesoscale imaging in freely behaving mice

Miniaturized head-mounted device for whole cortex mesoscale imaging in freely behaving mice

Design of a high-resolution light field miniscope for volumetric imaging in scattering tissue

The Photoconvertible Fluorescent Probe, CaMPARI, Labels Active Neurons in Freely-Moving Intact Adult Fruit Flies

Contact Info

Product

Resources

About