Biology subjects

Erdener, S. E.

Publications and source records attributed to Erdener, S. E..

11 recordsLinked to original sources

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

Mesoscale Functional Reorganization of Cortical Networks After Cortical Spreading Depression

BackgroundResting-state functional imaging is increasingly used to understand how cortical networks modulate and respond to pain. Awake imaging with a minimally invasive approach is key to observe the natural state of the brain. As migraine with aura, a common headache disorder, can be experimentally modeled by cortical spreading depressions (CSD) in rodents, it is essential to understand the impact of CSD on functional connectivity and network topology to find imaging cues of trigeminovascular activation and headache. MethodsWe used awake widefield intrinsic optical-signal imaging (IOSI) on optically cleared windows to non-invasively characterize the impact of CSDs on bihemispheric resting-state static and dynamic functional connectivity patterns and network topology. A subset of mice was chronically treated with amitriptyline to examine the effect of susceptibility to CSD on connectivity. After baseline imaging, CSD was triggered optogenetically and confirmed by laser speckle contrast imaging. A group of mice received intraperitoneal naproxen after CSD to suppress headache. IOSI was repeated at 30 minutes, 60 minutes, 4 hours, and 24 hours after CSD. The mouse grimace scale was scored at each time point for behavioral headache documentation. ResultsWe observed time-dependent changes in resting-state functional connectivity that were reversed by naproxen. Amitriptyline, a prophylactic migraine medication, decreased susceptibility to CSD and modified resting-state functional connectivity differently than controls. Network analysis with graph-theoretical methods revealed barrel and retrosplenial cortices as potential key players in trigeminal pain processing after CSD. Dynamic functional connectivity analysis demonstrated functional connectivity states, with fractional occupancy and mean dwell time of these states showing distinct CSD and pain-modulated states. A support vector machine was utilized to predict CSD-mediated dynamic connectivity changes in controls. ConclusionOur results bring insight into potentially headache-associated changes in resting-state cortical functional connectivity after CSD and how this functional reorganization is influenced by acute and chronic medications for migraine.

neuroscience↗

bioRxiv2026

Mapping Slow Speckle Dynamics to Probe Cellular Metabolic Activity In Vivo using Laser Speckle Contrast Imaging

SignificanceLaser speckle contrast imaging (LSCI) is widely used to measure blood flow, but speckle fluctuations may also encode biologically meaningful dynamics beyond perfusion. Foundational studies in dynamic light scattering (DLS) and micro-optical coherence tomography (OCT) have also demonstrated that slow coherent signal fluctuations can arise from energy-dependent intracellular motion in in vitro and ex vivo systems. Building upon these advances, recent work has shown that LSCI has the potential to detect slow speckle dynamics (SSD) correlated with cellular dynamics in vivo. However, the biophysical mechanisms underlying SSD in intact brain tissues remain insufficiently validated. Establishing a mechanistic bridge from controlled ex vivo and in vitro conditions to in vivo brain measurements is critical for translating speckle-based imaging beyond perfusion measurements to enable label-free assessment of cellular and metabolic activity in disease models. AimThe objective of this study is to investigate the biophysical origin of the SSD in vivo and evaluate its sensitivity to intracellular metabolic activity in brain tissue. ApproachWe utilize an epi-illumination LSCI system to measure speckle contrast as a function of camera exposure time and extract characteristic decorrelation time constants. SSD was investigated in acute mouse brain slices, where blood flow is absent, to eliminate vascular confounds. Cellular metabolism was systematically modulated using 2-deoxyglucose and glucose. Complementary in vivo measurements were performed to reveal SSDs response to hyperoxia and normoxia after ischemic stroke. ResultsSSD signals persisted in acute brain slices in the absence of blood flow. Inhibition of glycolysis significantly reduced SSD, while restoration of metabolic substrates partially recovered the signal. In in vivo measurements, SSD increased during hyperoxia compared to normoxia after ischemic stroke, suggesting increased oxygen-supported cellular metabolic activity. ConclusionsThese results indicate that SSD is sensitive to energy-dependent cellular processes closely tied to metabolic activity. SSD represents a previously uncharacterized, label-free in vivo optical contrast that enables assessment of cellular metabolic activity as well as vascular dynamics. This work establishes a mechanistic foundation for using SSD as a general optical marker of cellular viability in in vivo measurements.

neuroscience↗

bioRxiv2025

Torsional Force by Helical Pericytes Regulates Blood Flow in Downstream Capillaries

This study investigates the contractile properties of downstream capillaries, which are traditionally regarded as passive conduits, and addresses ongoing debates surrounding blood flow regulation. It is widely accepted that these capillaries passively dilate in response to increased blood flow in upstream microvessels, and that the helical pericytes located on them lack contractile capability, largely due to the absence of detectable -SMA expression. Challenging this prevailing view, we demonstrate that downstream capillary pericytes do express both -SMA and Myosin11, as shown using in situ hybridization on whole-mount intact retinas--unlike prior studies that relied on dissociated cells. Furthermore, Forster resonance energy transfer (FRET) analysis reveals that -SMA and Myosin11 are in sufficiently close proximity to permit actomyosin bridge cycling, a process essential for contraction. We also show that pericyte contraction can be inhibited by disrupting this molecular interaction. Distinct from the nodal constrictions caused by circular pericyte processes in upstream microvessels, we identify torsional contractions in the downstream capillaries in the retina of living mice using two-photon laser scanning microscopy (TPLSM), which regulates blood flow. These contractions provide direct evidence that downstream capillaries actively contribute to blood flow regulation. Notably, such contractions were overlooked in previous TPLSM studies that monitored only luminal diameter, unless the specialized analytical techniques we employed were applied. Our 3D modeling confirms that these torsional contractions correlate with the helical morphology of pericytes in downstream capillaries--a structure previously thought incapable of producing significant constrictive force. In conclusion, our findings provide direct evidence that downstream pericytes play an active role in regulating blood flow. They highlight a previously unrecognized mechanism--torsional contraction--that aligns with the helical structure of these pericytes and contributes to flow regulation in small-caliber capillaries located nearest to regions of high oxygen demand. TEASERDownstream Capillary Pericytes Express -SMA and Regulate Flow via Torsional Contraction

neuroscience↗

bioRxiv2024

Optical coherence tomography enables longitudinal evaluation of cell graft-directed remodeling in stroke lesions

Stem cell grafting can promote glial repair of adult stroke injuries during the subacute wound healing phase, but graft survival and glial repair outcomes are perturbed by lesion severity and mode of injury. To better understand how stroke lesion environments alter the functions of cell grafts, we employed optical coherence tomography (OCT) to longitudinally image mouse cortical photothrombotic ischemic strokes treated with allogeneic neural progenitor cell (NPC) grafts. OCT angiography, signal intensity, and signal decay resulting from optical scattering were assessed at multiple timepoints across two weeks in mice receiving an NPC graft or an injection of saline at two days after stroke. OCT scattering information revealed pronounced axial lesion contraction that naturally occurred throughout the subacute wound healing phase that was not modified by either NPC or saline treatment. By analyzing OCT signal intensity along the coronal plane, we observed dramatic contraction of the cortex away from the imaging window in the first week after stroke which impaired conventional OCT angiography but which enabled the detection of NPC graft-induced glial repair. There was moderate, but variable, NPC graft survival at photothrombotic strokes at two weeks which was inversely correlated with acute stroke lesion sizes as measured by OCT prior to treatment, suggesting a prognostic role for OCT imaging and reinforcing the dominant effect of lesion size and severity on graft outcome. Overall, our findings demonstrate the utility of OCT imaging for both tracking and predicting natural and treatment-directed changes in ischemic stroke lesion cores.

neuroscience↗

bioRxiv2024

VENTRAL HIPPOCAMPAL AND BASOLATERAL AMYGDALAR INPUTS TO DEEP, BUT NOT SUPERFICIAL LAYERS OF MEDIAL PREFRONTAL CORTEX UNDERLIE STRESS SUSCEPTIBILITY

Stress response is essential for adapting to an ever-changing environment. However, the mechanisms that render some individuals susceptible to stress are poorly understood. While chronic stress is known to induce dendritic atrophy and spine loss in medial prefrontal cortex (mPFC), its impact on synapses made by long-range projections terminating on the mPFC remains unknown. Here, we labeled synapses on male mouse mPFC dendrites formed by ventral hippocampus (VH), basolateral amygdala (BLA) and ventral tegmental area (VTA) long-range afferents using different-colored eGRASP constructs. We obtained multispectral 3D-images of the mPFC covering all cortical laminae, and automatically segmented the dendrites and synapses. In layer II/III, the relative abundances and spatial organizations of VH-mPFC and BLA-mPFC synapses changed similarly in stress resilient (SR) and stress susceptible (SS) mice when compared to stress naive (SN) mice. In layers Vb and VI, on the other hand, the percentage of BLA-mPFC increased and that of VH-mPFC decreased only in SS mice. Moreover, the distances of VH synapses to their corresponding closest BLA synapses decreased and the distances of BLA synapses to their corresponding closest VH synapses increased in the SS group. Consistently, the percentage of single dendritic segments receiving input from multiple brain regions increased in the SS group, suggesting that long-range synaptic inputs to deep layers of mPFC were disorganized in SS mice. Our findings demonstrate afferent- and lamina-specific differential reorganization of synapses between different stress phenotypes, suggesting specific roles for different long-range projections in mediating the stress response.

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↗

bioRxiv2019

Rapid disruption of the cortical microcirculation after mild traumatic brain injury

Traumatic brain injury (TBI) is a major source of cognitive deficits affecting millions annually. The bulk of human injuries are mild, causing little or no macroscopic damage to neural tissue, yet can still lead to long-term neuropathology manifesting months or years later. Although the cellular stressors that ultimately lead to chronic pathology are poorly defined, one notable candidate is metabolic stress due to reduced cerebral blood flow (CBF), which is common to many forms of TBI. Here we used high-resolution in vivo intracranial imaging in a rodent injury model to characterize deficits in the cortical microcirculation during both acute and chronic phases after mild TBI. We found that CBF dropped precipitously during immediate post-injury periods, decreasing to less than half of baseline levels within minutes and remaining suppressed for 1.5-2 hours. Repeated time-lapse imaging of the cortical microvasculature revealed further striking flow deficits in the capillary network, where 18% of vessels were completely occluded for extended periods after injury, and an additional >50% showed substantial stoppages. Decreased CBF was paralleled by extensive vasoconstriction that is likely to contribute to loss of flow. Our data indicate a major role for vascular dysfunction in even mild forms of TBI, and suggest that acute post-injury periods may be key therapeutic windows for interventions that restore flow and mitigate metabolic stress.

neuroscience↗

bioRxiv2019

Neutrophil-mediated dynamic capillary stalls in ischemic penumbra: persistent traffic jams after reperfusion contribute to injury

Ever since the introduction of thrombolysis and the subsequent expansion of endovascular treatments for acute ischemic stroke, it remains to be identified why the actual outcomes are less favorable despite recanalization. Here, by high spatio-temporal resolution imaging of capillary circulation in mice, we introduce the pathological phenomenon of dynamic flow stalls in cerebral capillaries, occurring persistently in the salvageable penumbra after recanalization. These stalls, which are distinct from permanent cellular plugs that can lead to no-flow, were temporarily and repetitively occurring in the capillary network, impairing the overall circulation like small focal traffic jams. In vivo microscopy in the ischemic penumbra revealed leukocytes traveling through capillary lumen or getting stuck, while red blood cell flow was being disturbed in the neighboring segments, within 3 hours after stroke onset. Stall dynamics could be modulated, by injection of an anti-Ly6G antibody specifically targeting neutrophils. By decreasing the number and duration of stalls, we were able to improve the blood flow in the penumbra within 2-24 hours after reperfusion, increase capillary oxygenation, decrease cellular damage and improve functional outcome. Thereby the dynamic microcirculatory stall phenomenon contributes to the ongoing penumbral injury and is a potential hyperacute stage mechanism adding on previous observations of detrimental effects of activated neutrophils in ischemic stroke.\n\nSignificanceThis work provides in vivo evidence that, even in perfused capillaries, abnormal capillary flow patterns in the form of dynamic stalls can contribute to ongoing tissue injury in the salvageable penumbra in very early hours of cerebral ischemia. These events resembling micro traffic jams in a complex road network, are mediated by passage of neutrophils through the microcirculation and persist despite recanalization of the occluded artery.

neuroscience↗

bioRxiv2019

Functional ultrasound speckle decorrelation-based velocimetry of the brain

A high-speed, contrast free, quantitative ultrasound velocimetry (vUS) for blood flow velocity imaging throughout the rodent brain is developed based on the normalized first order temporal autocorrelation function of the ultrasound field signal. vUS is able to quantify blood flow velocity in both transverse and axial directions, and is validated with numerical simulation, phantom experiments, and in vivo measurements. The functional imaging ability of vUS is demonstrated by monitoring blood flow velocity changes during whisker stimulation in awake mice. Compared to existing power Doppler and color Doppler-based functional ultrasound imaging techniques, vUS shows quantitative accuracy in estimating both axial and transverse flow speeds and resistance to acoustic attenuation and high frequency noise.

bioengineering↗

bioRxiv2019

Dynamic Laser Speckle Imaging

Utilizing a high-speed camera and recording back-scattered laser light at more than 20,000 frames per second, we introduce the first wide-field dynamic laser speckle imaging (DLSI) in which we are able to quantify the laser speckleintensity temporal auto-correlation function g2({tau}) for every pixel individually to obtain a quantitative image of the dynamics of the light scattering particles in the sample. The ability to directly and quantitatively measure the intensity auto-correlation function allows us to solve the problem of how to quantitatively interpret data measured by laser speckle contrast imaging (LSCI), multi-exposure laser speckle imaging (MESI) and laser Doppler flowmetry (LDF). The intensity auto-correlation function is related to the field temporal auto-correlation function g1({tau}), which has been quantitatively related to the dynamics of the light scattering particles including flowing red blood cells. The form of g1({tau}) depends on the amount of light scattering (i.e. single or multiple scattering) and the type of particle motion (i.e. ordered or unordered). Although these forms of the field correlation functions have been established for over 30 years, there is no agreement nor experimental support on what scattering and motion regimes are relevant for the varied biomedical applications. We thus apply DLSI to image cerebral blood flow in mouse through a cranial window and show that the generally accepted form of g1({tau}), is applicable only to visible surface vessels of a specific size (20 - 200m). We demonstrate that for flow in smaller vessels and in parenchymal regions that the proper g1({tau}) form corresponds with multiple scattering light and unordered motion which was never considered to be relevant for these techniques. We show that the wrong assumption for the field auto-correlation model results in a severe underestimation of flow changes when measuring blood flow changes during ischemic stroke. Finally, we describe how DLSI can be integrated with other laser speckle methods to guide model selection, or how it can be used by itself as a quantitative blood flow imaging technique.

bioengineering↗