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:10.1101/685909

Cited by 22 publications

(35 citation statements)

References 59 publications

(81 reference statements)

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“…Emerging techniques aim to challenge that limitation. For example, novel head-mounted microscopy (e.g., NINscope [100]) and two-photon imaging with expanded field of view (e.g., Trepan2P [101]) allow multiregion recordings. Widefield calcium imaging, while typically not having cellular resolution, can record mesoscale dynamics across multiple regions [102] and be used in freely Box 4.…”

Section: Advances In Multiregion Recording and Projection-mapping Tecmentioning

confidence: 99%

Circuit-Based Biomarkers for Mood and Anxiety Disorders

Xia

Kheirbek

2020

Trends in Neurosciences

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Mood and anxiety disorders are complex heterogeneous syndromes that manifest in dysfunctions across multiple brain regions, cell types, and circuits. Biomarkers using brain-wide activity patterns in humans have proven useful in distinguishing between disorder subtypes and identifying effective treatments. In order to improve biomarker identification, it is crucial to understand the basic circuitry underpinning brain-wide activity patterns. Leveraging a large repertoire of techniques, animal studies have examined roles of specific cell types and circuits in driving maladaptive behavior. Recent advances in multiregion recording techniques, data-driven analysis approaches, and machine-learning-based behavioral analysis tools can further push the boundary of animal studies and bridge the gap with human studies, to assess how brain-wide activity patterns encode and drive emotional behavior. Together, these efforts will allow identifying more precise biomarkers to enhance diagnosis and treatment. Distributed Neural Circuits Underly Mood and Anxiety Disorders Mood and anxiety disorders disrupt basic functions of individuals' lives, and are among the leading causes of disability [1]. In the USA, it is estimated that at a given timepoint, 10-20% of adults are impacted, and 20-30% of adults will experience a mood or anxiety disorder at some point in their lives (https://www.hcp.med.harvard.edu/ncs). However, most existing treatments are not effective [2,3]; largely due to a lack of clear understanding of disease etiology. The search for effective treatment is further complicated by the fact that mood and anxiety disorders are heterogeneous syndromes with various subtypes, where patients present diverse symptoms even for the same disorder, and often respond differently to the same treatment [4-7]. Highlights Mood and anxiety disorders are complex neural-circuit-based conditions that arise from dysfunctions across multiple cell types, brain regions, and circuits. Recent efforts in identifying circuit-based biomarkers using brain-wide activity patterns have shown promising results in stratifying disorder subtypes and identifying effective treatments for patients with mood and anxiety disorders.

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Section: Advances In Multiregion Recording and Projection-mapping Tecmentioning

confidence: 99%

Circuit-Based Biomarkers for Mood and Anxiety Disorders

Xia

Kheirbek

2020

Trends in Neurosciences

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“…While several head-mounted, miniaturized imaging devices have been developed for imaging neural activity in freely moving animals [26][27][28][29][30] , these devices are designed to perform cellular resolution imaging, and thus have small field of view (FOV, < 1 mm 2 ), limiting their application to imaging small brain regions. A head-mounted imaging device with a small FOV has recently been engineered for mesoscale imaging in rats 31 .…”

Section: Introductionmentioning

confidence: 99%

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

Rynes

Surinach

Linn

et al. 2020

Preprint

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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.

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“…First, one-photon photostimulation can be achieved with much lower power, providing optical control over many more neurons at power levels that are well below thresholds for tissue heating or brain damage. Second, the accessible volume for holographic two-photon photostimulation is limited by the intrinsic characters of the femtosecond pulse laser being used 17 , while one-photon systems can be readily scaled to much larger volumes with larger devices, addressing more brain surface and brain regions 18 . Third, unlike two-photon systems, which require physically large and highly energy-consuming lasers, one-photon systems can use small, lightweight diode lasers and compact optoelectronics so that the overall size and weight of the system can be minimized.…”

Section: Introductionmentioning

confidence: 99%

Three-dimensional Multi-site Random Access Photostimulation (3D-MAP)

Xue

Waller

Adesnik

et al. 2020

Preprint

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AbstractHigh precision optical control of neural ensemble activity is essential for understanding brain function and may ultimately revolutionize the treatment of brain disease. Currently only multiphoton holographic optogenetics achieves the requisite spatial resolution for precise neural network control. However, it suffers from critical drawbacks that limit the number of addressable neurons and prevent the development of implantable or wireless devices. Therefore, achieving high-resolution optogenetic control with one-photon activation is essential to catalyze a dramatic leap in spatiotemporally precise multi-site optogenetic technology for research and clinical use. To overcome this challenge, we developed a new light sculpting technique that can synthesize custom illumination patterns in 3D by rapidly projecting structured illumination patterns along with novel computational methods for precise optogenetic control, termed ‘3D-MAP’, for Three-dimensional Multi-site random Access Photostimulation. This technology enables the optogenetic synthesis of complex spatiotemporal sequences of neural activity in the intact brain. As a one-photon photostimulation technology, 3D-MAP can be widely adopted for custom optogenetic applications by the neuroscience research community, and opens the door to scalable, wireless high precision optical brain interfaces.

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NINscope: a versatile miniscope for multi-region circuit investigations

Cited by 22 publications

References 59 publications

Circuit-Based Biomarkers for Mood and Anxiety Disorders

Circuit-Based Biomarkers for Mood and Anxiety Disorders

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

Three-dimensional Multi-site Random Access Photostimulation (3D-MAP)

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