Biology subjects

Devor, A.

Publications and source records attributed to Devor, A..

At least 19 recordsLinked to original sources

bioRxiv2026

Dual-Mode Bio-CM2: Multimodal Computational Miniature Mesoscope for Fluorescence and Label-Free Imaging

Understanding biological function often requires complementary information on molecular identity, morphology, behavior, and physiology acquired simultaneously from the same specimen. Achieving this capability in miniature microscopes remains challenging because integrating multiple imaging contrasts typically increases optical complexity while compromising field of view (FOV), spatial resolution, or form factor. Here we present dual-mode Bio-CM2, a multimodal computational miniature mesoscope that simultaneously captures fluorescence and label-free reflectance through a shared optical architecture based on distributed computational optics. The system enables frame-interleaved, co-registered dual-mode imaging over a [~]7.5 x 10 mm2 FOV with [~]6 m lateral resolution. We demonstrate the versatility of dual-mode Bio-CM2 across diverse biological systems. In freely moving Caenorhabditis elegans, reflectance captures body posture and locomotor behavior that contextualize fluorescently labeled protein aggregates. In freely swimming larval zebrafish, reflectance captures whole-body morphology and swimming behavior, while fluorescence visualizes cardiac activity. In head-fixed mice, simultaneous fluorescence and reflectance imaging across the bilateral dorsal cortex provides complementary measurements of neuronal calcium activity and intrinsic hemodynamic signals. By integrating molecularly specific fluorescence with complementary reflectance contrast, dual-mode Bio-CM2 extends distributed computational optics into a scalable platform for multimodal miniature imaging.

bioengineering↗

bioRxiv2026

Bio-CM{superscript 2}: Distributed computational optics for cortex-widecellular imaging

Understanding distributed biological systems, particularly neural circuits, requires simultaneous cellular-resolution imaging across millimeter-scale fields of view (FOV). Existing miniature microscopes remain fundamentally constrained by trade-offs among FOV, spatial resolution, and optical complexity, limiting their ability to bridge cellular microscopy with cortex-scale imaging. Here we introduce distributed computational optics, a framework that distributes image formation across coordinated optical modules and computationally integrates their measurements into a unified image. We realize this framework in Bio-CM2, a computational miniature mesoscope that partitions the imaging field across four optical modules while converging their measurements onto a common image sensor. This architecture overcomes the aberration-scaling limitations of conventional miniature optics while avoiding the hardware complexity of multi-camera systems and the contrast degradation associated with optical multiplexing. Bio-CM2 achieves a 7.5 x 10 mm2 FOV while enabling cellular-resolution in vivo imaging at video rates. We demonstrate its utility through two complementary imaging modalities in head-fixed mice: cortex-wide functional vascular imaging, enabling simultaneous quantification of pial arteriole vasomotion and mesoscale hemodynamic functional connectivity, and cellular-resolution calcium imaging, resolving the activity of over 3,000 neurons together with mesoscale neuronal functional connectivity. We further demonstrate the versatility of the platform through cellular-resolution imaging of entire coronal mouse brain sections, population-scale imaging of freely behaving Caenorhabditis elegans, and odor-evoked calcium imaging of the main olfactory bulb in head-fixed mice, highlighting its broad applicability across diverse biological systems and imaging modalities. By overcoming the conventional trade-off between FOV and spatial resolution in a compact miniature platform, Bio-CM2 establishes distributed computational optics as a scalable framework for multiscale biological imaging.

bioengineering↗

bioRxiv2026

Visual gamma stimulation causes prolonged enhancement of low-frequency blood flow oscillations across cortical regions in mice

IntroductionGamma entrainment using sensory stimuli (GENUS) uses 40Hz-pulsed sensory stimuli to entrain neural activity in the gamma band (30-150Hz). However, the effect of GENUS on low-frequency vascular oscillations has not been fully explored. ObjectivesThe objective of this study is to elucidate the effect of GENUS on vasomotion in healthy mice and potential confounds for future application in disease studies. MethodsHead-fixed, awake C57Bl/6 mice (n=18; 9M 9F) aged between 18 to 60 weeks were subjected to white light of either 40Hz visual flicker (GENUS), or constant stimulus (control). Blood flow was imaged using laser speckle contrast imaging (LSCI) before, during, immediately after 1 hour of stimulus, and 30min after the stimulus termination. ResultsA linear mixed-effects model showed that GENUS enhanced the magnitude of 0.2-0.4Hz blood flow oscillations by 38% during stimulation and by 30% at 30 minutes after stimulation compared to control when controlled for age, sex, and other factors. The effect on vasomotion was distributed across many cortical regions not limited to visual areas and lasted beyond 24 hours post-stimulus. ConclusionThese results support the exploration of GENUS for increasing vasomotion in therapeutic contexts. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=186 SRC="FIGDIR/small/729102v1_ufig1.gif" ALT="Figure 1"> View larger version (67K): org.highwire.dtl.DTLVardef@1deee2eorg.highwire.dtl.DTLVardef@e71833org.highwire.dtl.DTLVardef@1e5c4f0org.highwire.dtl.DTLVardef@1e4832e_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2026

A pipeline for cell migration analysis in live-cell imaging data from human iPSC-derived forebrain assembloids.

During forebrain development, inhibitory interneurons and oligodendrocyte progenitor cells migrate long distances into the developing dorsal cortex. Human induced pluripotent stem cell-derived forebrain assembloids (FAs) provide direct experimental access to this migratory process in vitro. Using viral labeling to express yellow fluorescent protein (EYFP) and tandem-dimer tomato (tdTomato) driven by EF1 or SOX10 promoters, respectively, we tracked cells in FAs over 15-17h using spinning disk confocal microscopy. We developed an end-to-end processing pipeline for 4D volumetric imaging data, consisting of background subtraction and drift correction, manual cell coordinate tracking, and an analysis workflow to describe migratory cell behavior. Image preprocessing significantly improved data quality for subsequent manual tracking in datasets with heterogeneous labeling density and brightness. Trajectory analysis of 336 EYFP- and 337 tdTomato-labeled cells from twelve FAs indicates that most cells show super-diffusive directed motility. Our pipeline represents a key resource for cell tracking in FAs and similar three-dimensional platforms. This pipeline represents the first open tracking resource for iPSC-derived FAs and can be used as a ground-truth resource for the development of automated cell detection and tracking algorithms.

neuroscience↗

bioRxiv2026

High-Field Multinuclear MRI Reveals Sodium Relaxation Heterogeneity in Cortical Organoids

Sodium magnetic resonance imaging (23Na MRI) provides a unique opportunity to probe ionic microenvironments in neural tissue because sodium ions play central roles in membrane electrophysiology, ion transport, and cellular homeostasis. Unlike conventional proton ({superscript 1}H) MRI, which primarily reflects water distribution and tissue structure, {superscript 2}3Na MRI is sensitive to ionic compartmentation and quadrupolar interactions arising from the spin-3/2 nature of the sodium nucleus. However, sodium MRI remains technically challenging due to intrinsically low signal sensitivity and rapid biexponential relaxation, particularly when imaging small biological systems. Here, we establish a high-field multinuclear MRI platform for imaging human cerebral organoids at 14 Tesla. Cerebral organoids derived from human induced pluripotent stem cells provide a simplified three-dimensional neural tissue model that enables investigation of ionic microenvironments without vascular or systemic confounds. Using a dual-tuned {superscript 1}H/{superscript 2}3Na radiofrequency coil, we performed co-registered structural, diffusion, and sodium imaging of individual fixed organoids. High-resolution {superscript 1}H MRI (33-100 m) revealed pronounced microstructural heterogeneity, while multi-echo {superscript 2}3Na MRI (300-400 m) enabled voxel-wise characterization of quadrupolar relaxation behavior. Bi-exponential analysis of the sodium signal decay identified distinct relaxation components (T2*short {approx} 1 ms and T2*long {approx} 12 ms) and revealed spatial heterogeneity in sodium microenvironments across the organoid tissue. These results demonstrate the feasibility of quantitative sodium relaxometry in cortical organoids and establish a multinuclear imaging platform for investigating ionic microenvironment dynamics in three-dimensional neural tissue models.

bioengineering↗

bioRxiv2025

A neurorecording toolkit for longitudinal assessments of transplanted human cortical organoids in vivo

Human cortical organoids (hCOs) are three-dimensional neural cell aggregates that recapitulate certain structural and functional aspects of the developing human cortex. Xenotransplantation of hCOs into the rodent brain enables human-centric modeling of neurodevelopmental processes in a physiologically relevant environment. Here, we present a neurorecording toolkit for longitudinal structural and functional assessment of hCO xenografts as they mature in vivo. Single hCOs were implanted into the retrosplenial cortex of adult immunodeficient mice and monitored for up to 8 months. Optical coherence tomography was used for label-free imaging of xenograft vascularization and structure, enabling quantitative assessments of capillary density and graft volume. To probe neuronal activity, human neurons were labeled with a calcium sensor before implantation using either adeno-associated or lentivirus for sparse or dense neuronal labeling, respectively. Fluorescent imaging was conducted using two-photon, widefield, and swept confocally-aligned planar excitation microscopy for single cell, whole-graft, and volumetric calcium imaging, respectively. Results from these modalities indicate an increase in neuronal activity and synchronicity over time during in vivo graft maturation. Further, we chronically implanted surface graphene microelectrode arrays (gMEAs) and performed recordings of xenograft and host local field potential signals simultaneously with 2P calcium imaging, confirming the spatial localization and human origin of electrical signals recorded at the xenograft surface.

neuroscience↗

bioRxiv2025

Distinct Ca2+ signatures of leptomeningeal fibroblast subgroups in awake mouse brains in health and inflammation

The leptomeninges, composed of the arachnoid mater, and pia mater, contains distinct subgroups of fibroblasts that differ in location and transcriptomic profiles. These fibroblasts contribute to the blood-cerebrospinal fluid barrier under physiological conditions, participate in fibrosis, and support blood-brain barrier integrity during injury and disease. However, their Ca2+ signaling profiles and underlying mechanisms in health and disease remain poorly understood. In this study, we divided leptomeningeal fibroblasts into three subgroups based on their locations: arachnoid fibroblasts, pia mater fibroblasts and perivascular fibroblasts. We employed two-photon microscopy in awake transgenic mice expressing Ca{superscript 2} indicators in leptomeningeal fibroblasts to investigate spontaneous and behaviorally evoked Ca{superscript 2} transients across different fibroblast subgroups. We found that each subgroup exhibits a distinct Ca{superscript 2} activity profile, with pia mater fibroblasts showing the highest-amplitude Ca{superscript 2} transients. Moreover, these fibroblasts displayed unique responses to both whisker air-puff stimulation and locomotion. We further demonstrated, using a chronically implanted cannula beneath the cranial window, that locomotion-associated vasodilation is followed by TRPV4 channel-mediated fibroblast Ca{superscript 2} elevations. Finally, systemic inflammation induced by lipopolysaccharide (LPS) reduced spontaneous Ca{superscript 2} transients in pia mater fibroblasts, likely due to macrophage infiltration following the inflammatory response. For the first time, this study characterizes spontaneous and behaviorally evoked Ca{superscript 2} dynamics in distinct leptomeningeal fibroblast subgroups in awake animals, providing novel insights into the functional roles of leptomeningeal fibroblasts in the healthy and diseased brain.

neuroscience↗

bioRxiv2024

Neurovascular Impulse Response Function (IRF) during spontaneous activity differentially reflects intrinsic neuromodulation across cortical regions

Ascending neuromodulatory projections from deep brain nuclei generate internal brain states that differentially engage specific neuronal cell types. Because neurovascular coupling is cell-type specific and neuromodulatory transmitters have vasoactive properties, we hypothesized that the impulse response function (IRF) linking spontaneous neuronal activity with hemodynamics would depend on neuromodulation. To test this hypothesis, we used optical imaging to measure (1) release of neuromodulatory transmitters norepinephrine (NE) or acetylcholine (ACh), (2) Ca2+ activity of local cortical neurons, and (3) changes in hemoglobin concentration and oxygenation across the dorsal surface of cerebral cortex during spontaneous neuronal activity in awake mice. A canonical convolution model with a global, stationary IRF (i.e., the convolution kernel) describing evolution of total hemoglobin (HbT, reflective of dilation dynamics) with respect to Ca2+, resulted in a poor fit to the data. However, the HbT time-course was well predicted, pixel-by-pixel, by a weighted sum of Ca2+ and NE time-courses. Consistent with this result, modeling HbT as a weighted sum of stationary Ca2+ - and NE-specific IRFs (IRFCa2+ and IRFNE) convolved with the respective time-courses dramatically improved the fit compared to the global IRF. IRFCa2+ and IRFNE, estimated from the data, were positive and negative, respectively. In contrast to NE, ACh was largely redundant with Ca2+ and therefore did not improve HbT estimation. Because NE covaried with arousal, we observed instances of the diminished hemodynamic coherence between cortical regions during high arousal despite coherent behavior of the underlying neuronal Ca2+ activity. We conclude that while neurovascular coupling with respect to neuronal Ca2+ is a dynamic and seemingly complex phenomenon, hemodynamic fluctuations can be captured by a simple linear model with stationary IRFs with respect to the underlying dilatory and constrictive forces. In the current study, these forces were captured by the positive IRFCa2+ (dilation) and negative IRFNE (constriction). Without accounting for NE neuromodulation and the associated vasoconstriction, diminished hemodynamic coherence, commonly referred to as "functional (dys)connectivity" in BOLD fMRI studies, can be falsely interpreted as neuronal desynchronizations.

neuroscience↗

bioRxiv2024

Visual stimulation drives retinotopic acetylcholine release in the mouse visual cortex

Cholinergic signaling is involved with a variety of brain functions including learning and memory, attention, and behavioral state modulation. The spatiotemporal characteristics of neocortical acetylcholine (ACh) release in response to sensory inputs are poorly understood, but a lack of intra-region topographic organization of cholinergic projections from the basal forebrain has suggested diffuse release patterns and volume transmission. Here, we use mesoscopic imaging of fluorescent ACh sensors to show that visual stimulation results in ACh release patterns that conform to a retinotopic map of visual space in the mouse primary visual cortex, suggesting new modes of functional cholinergic signaling in cortical circuits.x

neuroscience↗

bioRxiv2023

High-resolution awake mouse fMRI at 14 Tesla

High-resolution awake mouse fMRI remains challenging despite extensive efforts to address motion-induced artifacts and stress. This study introduces an implantable radiofrequency (RF) surface coil design that minimizes image distortion caused by the air/tissue interface of mouse brains while simultaneously serving as a headpost for fixation during scanning. Furthermore, this study provides a thorough acclimation method used to accustom animals to the MRI environment minimizing motion induced artifacts. Using a 14T scanner, high-resolution fMRI enabled brain- wide functional mapping of visual and vibrissa stimulation at 100x100x200{micro}m resolution with a 2s per frame sampling rate. Besides activated ascending visual and vibrissa pathways, robust BOLD responses were detected in the anterior cingulate cortex upon visual stimulation and spread through the ventral retrosplenial area (VRA) with vibrissa air-puff stimulation, demonstrating higher-order sensory processing in association cortices of awake mice. In particular, the rapid hemodynamic responses in VRA upon vibrissa stimulation showed a strong correlation with the hippocampus, thalamus, and prefrontal cortical areas. Cross-correlation analysis with designated VRA responses revealed early positive BOLD signals at the contralateral barrel cortex (BC) occurring 2 seconds prior to the air-puff in awake mice with repetitive stimulation, which was not detected using a randomized stimulation paradigm. This early BC activation indicated a learned anticipation through the vibrissa system and association cortices in awake mice under continuous training of repetitive air-puff stimulation. This work establishes a high-resolution awake mouse fMRI platform, enabling brain-wide functional mapping of sensory signal processing in higher association cortical areas. Significance StatementThis awake mouse fMRI platform was developed by implementing an advanced implantable radiofrequency (RF) coil scheme, which simultaneously served as a headpost to secure the mouse head during scanning. A thorough acclimation method was used to accustom animals to the MRI environment minimizing motion induced artifacts. The ultra-high spatial resolution (100x100x200{micro}m) BOLD fMRI enabled the brain-wide mapping of activated visual and vibrissa systems during sensory stimulation in awake mice, including association cortices, e.g. anterior cingulate cortex and retrosplenial cortex, for high order sensory processing. Also, the activation of barrel cortex at 2 s prior to the air-puff indicated a learned anticipation of awake mice under continuous training of the repetitive vibrissa stimulation.

neuroscience↗

bioRxiv2023

Widefield in vivo imaging system with two fluorescence and two reflectance channels, a single sCMOS detector, and shielded illumination

SignificanceWidefield microscopy of the entire dorsal part of mouse cerebral cortex enables large-scale ("mesoscopic") imaging of different aspects of neuronal activity with spectrally compatible fluorescent indicators as well as hemodynamics via oxy- and deoxyhemoglobin absorption. Versatile and cost-effective imaging systems are needed for large-scale, color-multiplexed imaging of multiple fluorescent and intrinsic contrasts. AimDevelop a system for mesoscopic imaging of two fluorescent and two reflectance channels. ApproachExcitation of red and green fluorescence is achieved through epi-illumination. Hemoglobin absorption imaging is achieved using 525- and 625-nm LEDs positioned around the objective lens. An aluminum hemisphere placed between objective and cranial window provides diffuse illumination of the brain. Signals are recorded sequentially by a single sCMOS detector. ResultsWe demonstrate performance of our imaging system by recording large-scale spontaneous and stimulus-evoked neuronal, cholinergic, and hemodynamic activity in awake head-fixed mice with a curved "crystal skull" window expressing the red calcium indicator jRGECO1a and the green acetylcholine sensor GRABACh3.0. Shielding of illumination light through the aluminum hemisphere enables concurrent recording of pupil diameter changes. ConclusionsOur widefield microscope design with single camera can be used to acquire multiple aspects of brain physiology and is compatible with behavioral readouts of pupil diameter.

neuroscience↗

bioRxiv2023

Multi-modal microvascular cerebral blood flow velocity mapping with 14T single-vessel MRI and optical microscopy in the mouse brain

In this study, we imaged the same penetrating cortical vessels in a mouse using ultrahigh field single-vessel MRI at 14 T and high-resolution optical microscopy imaging. The optical imaging was performed through a chronic sealed cranial window, while the single-vessel MRI was facilitated by a custom-designed, chronically implanted radiofrequency coil surrounding the window. The MRI and optical imaging were performed sequentially focused on the same penetrating cortical arterioles and surfacing venules within the whisker barrel cortex. With MRI, we obtained high-resolution multi-gradient echo (MGE) images and single-vessel phase contrast (PC) velocity maps. With optical imaging, we acquired microvascular angiograms using 2-Photon Microscopy (2PM) and Optical Coherence Tomography (OCT) and measured the blood flow velocity using Dynamic Light Scattering OCT (DLS-OCT). The MGE images, PC-based MRI velocity maps, OCT angiograms, and DLS-OCT velocity maps were coregistered with the 2PM microvascular angiograms. Using these tools, we cross-validated blood flow velocity in the penetrating cortical arterioles and surfacing venules measured by single-vessel MRI and OCT at rest. Our novel method demonstrates the possibility of combining ultrahigh field single-vessel MRI and high-resolution optical methods (e.g., 2PM and OCT) for studying brain structure and function with single microvessel precision.

bioengineering↗

bioRxiv2023

Aerobic exercise reverses aging-induced depth-dependent decline in cerebral microcirculation

Aging is a major risk factor for cognitive impairment. Aerobic exercise benefits brain function and may promote cognitive health in older adults. However, underlying biological mechanisms across cerebral gray and white matter are poorly understood. Selective vulnerability of the white matter to small vessel disease and a link between white matter health and cognitive function suggests a potential role for responses in deep cerebral microcirculation. Here, we tested whether aerobic exercise modulates cerebral microcirculatory changes induced by aging. To this end, we carried out a comprehensive quantitative examination of changes in cerebral microvascular physiology in cortical gray and subcortical white matter in mice (3-6 vs. 19-21 months old), and asked whether and how exercise may rescue age-induced deficits. In the sedentary group, aging caused a more severe decline in cerebral microvascular perfusion and oxygenation in deep (infragranular) cortical layers and subcortical white matter compared with superficial (supragranular) cortical layers. Five months of voluntary aerobic exercise partly renormalized microvascular perfusion and oxygenation in aged mice in a depth-dependent manner, and brought these spatial distributions closer to those of young adult sedentary mice. These microcirculatory effects were accompanied by an improvement in cognitive function. Our work demonstrates the selective vulnerability of the deep cortex and subcortical white matter to aging-induced decline in microcirculation, as well as the responsiveness of these regions to aerobic exercise.

neuroscience↗

bioRxiv2022

Imaging through Windansee electrode arrays reveals a small fraction of local neurons following surface MUA

Prior studies have shown that neuronal spikes can be recorded with microelectrode arrays placed on the cortical surface. However, the etiology of these spikes remains unclear. Because the top cortical layer (layer 1) contains very few neuronal cell bodies, it has been proposed that these spikes originate from neurons with cell bodies in layer 2. To address this question, we combined two-photon calcium imaging with electrophysiological recordings from the cortical surface in awake mice using chronically implanted PEDOT:PSS electrode arrays on transparent parylene C substrate. Our electrode arrays (termed Windansee) were integrated with cortical windows offering see-through optical access while also providing measurements of local field potentials (LFP) and multiunit activity (MUA) from the cortical surface. To enable longitudinal data acquisition, we have developed a mechanical solution for installation, connectorization, and protection of Windansee devices aiming for an unhindered access for high numerical aperture microscope objectives and a lifetime of several months while worn by a mouse. Contrary to the common notion, our measurements revealed that only a small fraction of layer 2 neurons from the sampled pool (~13%) faithfully followed MUA recorded from the surface above the imaging field-of-view. Surprised by this result, we turned to computational modeling for an alternative explanation of the MUA signal. Using realistic modeling of neurons with back-propagating dendritic properties, we computed the extracellular action potential at the cortical surface due to firing of local cortical neurons and compared the result to that due to axonal inputs to layer 1. Assuming the literature values for the cell/axon density and firing rates, our modeling results show that surface MUA due to axonal inputs is over an order of magnitude larger than that due to firing of layer 2 pyramidal neurons. Thus, a combination of surface MUA recordings with two-photon calcium imaging can provide complementary information about the input to a cortical column and the local circuit response. Cortical layer I plays an important role in integration of a broad range of cortico-cortical, thalamocortical and neuromodulatory inputs. Therefore, detecting their activity as MUA while combining electrode recording with two-photon imaging using optically transparent surface electrode arrays would facilitate studies of the input/output relationship in cortical circuits, inform computational circuit models, and improve the accuracy of the next generation brain-machine interfaces.

neuroscience↗

bioRxiv2022

A lone spike in blood glucose can enhance the thrombo-inflammatory response in cortical venules

How transient hyperglycemia contributes to cerebro-vascular disease has been a challenge to study under controlled conditions. We present an approach to model luminal vessel thrombo-inflammation using amplified, ultrashort laser-pulses to physically disrupt brain-venule endothelium. Vessel disruption in conjunction with transient hyperglycemia from a single injection of metabolically active D-glucose results in real-time responses to venule damage that include rapid serum extravasation, platelet aggregation, and neutrophil recruitment, in normal mice. In contrast, vessel thrombo-inflammation following laser-induced vessel disruption is significantly reduced in mice injected with metabolically inert L-glucose. Thrombo-inflammation is pharmacologically ameliorated by a platelet inhibitor, by a scavenger of reactive oxygen species, or by a nitric oxide donor. For comparison, in diabetic mice injured vessel thrombo-inflammatory responses are also reduced by restoration of normo-glycemia. Our approach provides a controlled method to probe synergies of transient metabolic and physical vascular perturbations and reveals new aspects of brain pathophysiology.

neuroscience↗

bioRxiv2022

Multimodal monitoring of human cortical organoids implanted in mice using transparent graphene microelectrodes reveal functional connection between organoid and mouse visual cortex

Human cortical organoids, three-dimensional neuronal cell cultures derived from human induced pluripotent stem cells, have recently emerged as promising models of human brain development and dysfunction. Transplantation of human brain organoids into the mouse brain has been shown to be a successful in vivo model providing vascularization for long term chronic experiments. However, chronic functional connectivity and responses evoked by external sensory stimuli has yet to be demonstrated, due to limitations of chronic recording technologies. Here, we develop an experimental paradigm based on transparent graphene microelectrode arrays and two-photon imaging for longitudinal, multimodal monitoring of human organoids transplanted in the mouse cortex. The transparency of graphene microelectrodes permits visual and optical inspection of the transplanted organoid and the surrounding cortex throughout the chronic experiments where local field potentials and multi-unit activity (MUA) are recorded during spontaneous activity and visual stimuli. These experiments reveal that visual stimuli evoke electrophysiological responses in the organoid, matching the responses from the surrounding cortex. Increases in the power of the gamma and MUA bands as well as phase locking of MUA events to slow oscillations evoked by visual stimuli suggest functional connectivity established between the human and mouse tissue. Optical imaging through the transparent microelectrodes shows vascularization of the organoids. Postmortem histological analysis exhibits morphological integration and synaptic connectivity with surrounding mouse cortex as well as migration of organoid cells into the surrounding cortex. This novel combination of stem cell and neural recording technologies could serve as a unique platform for comprehensive evaluation of organoids as models of brain development and dysfunction and as personalized neural prosthetics to restore lost, degenerated, or damaged brain regions.

neuroscience↗

bioRxiv2022

Targeted photothrombotic stroke leads to disruptions in neurovascular coupling

Functional neuroimaging, which measures hemodynamic responses to brain activity, has great potential for monitoring stroke patients. However, the neurophysiological interpretations of these hemodynamic signals remain a challenge as the stroke is likely to alter both neural activity and neurovascular coupling. To address this challenge, we simultaneously captured neural activity, through fluorescence calcium imaging, and hemodynamics, through intrinsic optical signal imaging, during longitudinal stroke recovery. We found that photothrombotic stroke to somatosensory forelimb region altered neurovascular coupling in the acute phase (2 days and 1 week post-stroke) within the affected forelimb and peri-infarct regions. Neurovascular coupling was reestablished in the chronic phase (4 weeks post-stroke), and acute recovery of neurovascular coupling predicted sensorimotor function. Stroke also resulted in increases in the power of global brain oscillations, which showed distinct patterns between calcium and hemodynamics. Increased calcium excitability in the contralesional hemisphere was associated with increased intrahemispheric connectivity. Additionally, acute increases in hemodynamic oscillations were associated with improved sensorimotor outcomes. TeaserAcute ischemic stroke leads to neurovascular uncoupling and the extent of early recoupling predicts sensorimotor recovery.

physiology↗

bioRxiv2021

Microscopic Quantification of Oxygen Consumption across Cortical Layers

The cerebral cortex is organized in cortical layers that differ in their cellular density, composition, and wiring. Cortical laminar architecture is also readily revealed by staining for cytochrome oxidase - the last enzyme in the respiratory electron transport chain located in the inner mitochondrial membrane. It has been hypothesized that a high-density band of cytochrome oxidase in cortical layer IV reflects higher oxygen consumption under baseline (unstimulated) conditions. Here, we tested the above hypothesis using direct measurements of the partial pressure of O2 (pO2) in cortical tissue by means of 2-photon phosphorescence lifetime microscopy (2PLM). We revisited our previously developed method for extraction of the cerebral metabolic rate of O2 (CMRO2) based on 2-photon pO2 measurements around diving arterioles and applied this method to estimate baseline CMRO2 in awake mice across cortical layers. To our surprise, our results revealed a decrease in baseline CMRO2 from layer I to layer IV. This decrease of CMRO2 with cortical depth was paralleled by an increase in tissue oxygenation. Higher baseline oxygenation and cytochrome density in layer IV may serve as an O2 reserve during surges of neuronal activity or certain metabolically active brain states rather than baseline energy needs. Our study provides the first quantification of microscopically resolved CMRO2 across cortical layers as a step towards informed interpretation and modeling of cortical-layer-specific Blood Oxygen Level Dependent (BOLD) functional Magnetic Resonance Imaging (fMRI) signals.

neuroscience↗