Cortex-wide neural interfacing via transparent polymer skulls

Ghanbari, Leila; Carter, Russell E.; Rynes, Matthew; Dominguez, Judith; Chen, Gang; Naik, Anant; Hu, Jia; Sagar, Abdul Kader; Haltom, Lenora; Mossazghi, Nahom; Gray, Madelyn M.; West, Sarah; Eliceiri, Kevin W.; Ebner, Timothy J.; Kodandaramaiah, Suhasa B.

doi:10.1101/387142

Cited by 5 publications

(6 citation statements)

References 81 publications

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“…Mice were head-fixed over a disk treadmill that allowed for spontaneous locomotion (Fig. 1A), and wide-field Ca 2+ imaging performed through an implanted polymer skull (Ghanbari et al 2019) (Fig. 1B).…”

Section: Resultsmentioning

confidence: 99%

“…Eight (5 male, 3 female) transgenic mice expressing GCaMP6f primarily in excitatory pyramidal neurons of the cerebral cortex (C57BL/6J, Thy1-GCaMP6f Jackson laboratories JAX 024339) were used (Dana et al 2014). To obtain optical access to a large region of the dorsal cerebral cortex, we implanted morphologically conformant windows made from transparent polymer (Ghanbari et al 2019). Prior to surgery, animals were administered slow release buprenorphine (2mg/kg s.c.) and then anesthetized with isoflurane (5% induction, 0.5-3% maintenance).…”

Section: Methodsmentioning

confidence: 99%

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Wide-Field Calcium Imaging of Dynamic Cortical Networks During Locomotion

West

Popa

Carter

et al. 2020

Preprint

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ABSTRACTBehavior results in widespread activation of the cerebral cortex. To fully understanding the cerebral cortex’s role in behavior therefore requires a mesoscopic level description of the cortical regions engaged and their functional interactions. Mesoscopic imaging of Ca2+ fluorescence through transparent polymer skulls implanted on transgenic Thy1-GCaMP6f mice reveals widespread activation of the cerebral cortex during locomotion, including not just primary motor and somatosensory regions but also premotor, auditory, retrosplenial, and visual cortices. To understand these patterns of activation, we used spatial Independent Component Analysis (sICA) that segmented the dorsal cortex of individual mice into 20-22 Independent Components (ICs). The resulting ICs are highly consistent across imaging sessions and animals. Using the time series of Ca2+ fluorescence in each IC, we examined the changes in functional connectivity from rest to locomotion. Compared to rest, functional connectivity increases prior to and at the onset of locomotion. During continued walking, a global decrease in functional connectivity develops compared to rest that uncovers a distinct, sparser network in which ICs in secondary motor areas increase their correlations with more posterior ICs in somatosensory, motor, visual, and retrosplenial cortices. Eigenvector centrality analysis demonstrates that ICs located in premotor areas increase their influence on the network during locomotion while ICs in other regions, including somatosensory and primary motor, decrease in importance. We observed sequential changes in functional connectivity across transitions between rest and locomotion, with premotor areas playing an important role in coordination of computations across cortical brain regions.SIGNIFICANCEBehavior such as locomotion requires the coordination of multiple cerebral cortical regions to accurately navigate the external environment. However, it is unclear how computations from various regions are integrated to produce a single, coherent behavioral output. Here, wide-field, epifluorescence Ca2+ imaging across the dorsal cerebral cortex reveals the changing functional interactions among cortical regions during the transition from rest to locomotion. While functional connectivity among most cortical nodes primarily decreases from rest to locomotion, a well-defined network of increased correlations emerges between premotor and other cortical regions with an increase in the importance of the premotor cortex to the network. The results suggest that the role of the premotor areas in locomotion involves coordinating interactions among different cortical regions.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Wide-Field Calcium Imaging of Dynamic Cortical Networks During Locomotion

West

Popa

Carter

et al. 2020

Preprint

Self Cite

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“…through the intact scalp (estimated thickness 0.5 mm) and skull (estimated thickness 0.4-0.6 mm) 30,31 .…”

Section: Resultsmentioning

confidence: 99%

Deep tissue optoacoustic localization microangiography

Robin

et al. 2021

Preprint

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Super-resolution methods have been developed to overcome physical diffraction limits of optical and ultrasound imaging techniques. Hybrid optoacoustic imaging approaches share the rich functional and molecular contrast advantages of optical methods while additionally attaining centimeter-scale penetration into living tissues due to reduced ultrasound scattering. The application of super-resolution principles for enhancing the optoacoustic imaging performance deep in mammalian tissues has so far been impeded by the high density of strongly absorbing red blood cells. Herein, we demonstrate three-dimensional microangiography of deep mouse brain beyond the acoustic diffraction limit (<20 µm resolution) through the intact scalp and skull via optoacoustic localization of sparsely-distributed highly absorbing microparticles. This was enabled by devising 5 µm sized extremely absorbing dichloromethane microdroplets exhibiting four orders of magnitude higher optical absorption than red blood cells at near-infrared wavelengths, thus facilitating in vivo compatibility and single particle sensitivity in the presence of highly absorbing blood background. Accurate mapping of the blood flow velocity within microvascular structures was also accomplished with a dedicated high-frame-rate volumetric optoacoustic tomography system. We further show that the detected optoacoustic signal intensities from the localized particles may serve for estimating the light fluence distribution within optically heterogeneous tissues, a long-standing quantification challenge in biomedical optics. Given the intrinsic sensitivity of optoacoustics to various functional, metabolic and molecular events in living tissues, this new approach paves the way for non-invasive deep-tissue microscopic observations with unrivaled resolution, contrast and speed.

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“…Headpost implant design was adapted from Ghanbari et al [62], and consists of a custom-made Titanium or Stainless-steel head-plate, a 3D-printed frame, and three 0-80 screws to hold the frame to the head-plate. We fabricated the head-plate with Titanium or Stainless-steel plate (McMaster-Carr) using a waterjet system (OMax), and 3D printed the frame using a ProJet MJP 2500 (3D Systems).…”

Section: Headpost Implant and Cranial Window Designmentioning

confidence: 99%

In vivo imaging with a flat, lensless microscope

Adams

Yan

et al. 2021

Preprint

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Lenless microscopes that form images using simple, compact optics, along with associated computational algorithms provide several advantages: small, inexpensive form factors, large fields of view (FOV), and the ability to refocus an image after capture. To date, however, lensless microscopy has yet to be demonstrated for in vivo biological imaging. The primary challenge with in vivo bio-imaging is these dense, low-contrast scenes cannot be accurately reconstructed with existing lensless techniques. To overcome this challenge, we designed an optical phase mask that creates a point-spread function consisting of high-contrast contours with a broad spatial frequency spectrum. Here we show that this “contour” phase mask enables in vivo imaging where previous lensless imaging technologies have failed. As a proof of concept, we demonstrate 3D imaging of a behaving invertebrate, functional calcium imaging in mouse cortex, and in vivo imaging of microvasculature in the human oral mucosa. Together these results demonstrate the ability of lensless imaging to operate in realistic biological imaging applications ranging from pre-clinical animal models to clinical biomedical imaging. Overall, this “Bio-FlatScope” is a clinically relevant imaging technique with advantages of 3D computational refocusing in a low-cost, small form factor that is useful for low-resource settings and difficult-to-reach areas of the body.

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Cortex-wide neural interfacing via transparent polymer skulls

Cited by 5 publications

References 81 publications

Wide-Field Calcium Imaging of Dynamic Cortical Networks During Locomotion

Wide-Field Calcium Imaging of Dynamic Cortical Networks During Locomotion

Deep tissue optoacoustic localization microangiography

In vivo imaging with a flat, lensless microscope

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