Person: Devor, Anna
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Devor
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Anna
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Devor, Anna
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Publication Deep 2-photon imaging and artifact-free optogenetics through transparent graphene microelectrode arrays(Nature Publishing Group UK, 2018) Thunemann, Martin; Lu, Yichen; Liu, Xin; Kılıç, Kıvılcım; Desjardins, Michèle; Vandenberghe, Matthieu; Sadegh, Sanaz; Saisan, Payam A.; Cheng, Qun; Weldy, Kimberly L.; Lyu, Hongming; Djurovic, Srdjan; Andreassen, Ole A.; Dale, Anders M.; Devor, Anna; Kuzum, DuyguRecent advances in optical technologies such as multi-photon microscopy and optogenetics have revolutionized our ability to record and manipulate neuronal activity. Combining optical techniques with electrical recordings is of critical importance to connect the large body of neuroscience knowledge obtained from animal models to human studies mainly relying on electrophysiological recordings of brain-scale activity. However, integration of optical modalities with electrical recordings is challenging due to generation of light-induced artifacts. Here we report a transparent graphene microelectrode technology that eliminates light-induced artifacts to enable crosstalk-free integration of 2-photon microscopy, optogenetic stimulation, and cortical recordings in the same in vivo experiment. We achieve fabrication of crack- and residue-free graphene electrode surfaces yielding high optical transmittance for 2-photon imaging down to ~ 1 mm below the cortical surface. Transparent graphene microelectrode technology offers a practical pathway to investigate neuronal activity over multiple spatial scales extending from single neurons to large neuronal populations.Publication Neurovascular Network Explorer 1.0: a database of 2-photon single-vessel diameter measurements with MATLAB® graphical user interface(Frontiers Media S.A., 2014) Sridhar, Vishnu B.; Tian, Peifang; Dale, Anders M.; Devor, Anna; Saisan, Payam A.We present a database client software—Neurovascular Network Explorer 1.0 (NNE 1.0)—that uses MATLAB® based Graphical User Interface (GUI) for interaction with a database of 2-photon single-vessel diameter measurements from our previous publication (Tian et al., 2010). These data are of particular interest for modeling the hemodynamic response. NNE 1.0 is downloaded by the user and then runs either as a MATLAB script or as a standalone program on a Windows platform. The GUI allows browsing the database according to parameters specified by the user, simple manipulation and visualization of the retrieved records (such as averaging and peak-normalization), and export of the results. Further, we provide NNE 1.0 source code. With this source code, the user can database their own experimental results, given the appropriate data structure and naming conventions, and thus share their data in a user-friendly format with other investigators. NNE 1.0 provides an example of seamless and low-cost solution for sharing of experimental data by a regular size neuroscience laboratory and may serve as a general template, facilitating dissemination of biological results and accelerating data-driven modeling approaches.Publication Cell type specificity of neurovascular coupling in cerebral cortex(eLife Sciences Publications, Ltd, 2016) Uhlirova, Hana; Kılıç, Kıvılcım; Tian, Peifang; Thunemann, Martin; Desjardins, Michèle; Saisan, Payam A; Sakadzic, Sava; Ness, Torbjørn V; Mateo, Celine; Cheng, Qun; Weldy, Kimberly L; Razoux, Florence; Vandenberghe, Matthieu; Cremonesi, Jonathan A; Ferri, Christopher GL; Nizar, Krystal; Sridhar, Vishnu B; Steed, Tyler C; Abashin, Maxim; Fainman, Yeshaiahu; Masliah, Eliezer; Djurovic, Srdjan; Andreassen, Ole A; Silva, Gabriel A; Boas, David; Kleinfeld, David; Buxton, Richard B; Einevoll, Gaute T; Dale, Anders M; Devor, AnnaIdentification of the cellular players and molecular messengers that communicate neuronal activity to the vasculature driving cerebral hemodynamics is important for (1) the basic understanding of cerebrovascular regulation and (2) interpretation of functional Magnetic Resonance Imaging (fMRI) signals. Using a combination of optogenetic stimulation and 2-photon imaging in mice, we demonstrate that selective activation of cortical excitation and inhibition elicits distinct vascular responses and identify the vasoconstrictive mechanism as Neuropeptide Y (NPY) acting on Y1 receptors. The latter implies that task-related negative Blood Oxygenation Level Dependent (BOLD) fMRI signals in the cerebral cortex under normal physiological conditions may be mainly driven by the NPY-positive inhibitory neurons. Further, the NPY-Y1 pathway may offer a potential therapeutic target in cerebrovascular disease. DOI: http://dx.doi.org/10.7554/eLife.14315.001Publication Neurovascular Network Explorer 2.0: A Database of 2-Photon Single-Vessel Diameter Measurements from Mouse SI Cortex in Response To Optogenetic Stimulation(Frontiers Media S.A., 2017) Uhlirova, Hana; Tian, Peifang; Kılıç, Kıvılcım; Thunemann, Martin; Sridhar, Vishnu B.; Bartsch, Hauke; Dale, Anders M.; Devor, Anna; Saisan, Payam A.Publication The BRAIN Initiative(Society of Photo-Optical Instrumentation Engineers, 2014) Devor, Anna; Roe, Anna W.; Mahadevan-Jansen, Anita; Boas, DavidPublication Modeling of Cerebral Oxygen Transport Based on In vivo Microscopic Imaging of Microvascular Network Structure, Blood Flow, and Oxygenation(Frontiers Media S.A., 2016) Gagnon, Louis; Smith, Amy F.; Boas, David; Devor, Anna; Secomb, Timothy W.; Sakadzic, SavaOxygen is delivered to brain tissue by a dense network of microvessels, which actively control cerebral blood flow (CBF) through vasodilation and contraction in response to changing levels of neural activity. Understanding these network-level processes is immediately relevant for (1) interpretation of functional Magnetic Resonance Imaging (fMRI) signals, and (2) investigation of neurological diseases in which a deterioration of neurovascular and neuro-metabolic physiology contributes to motor and cognitive decline. Experimental data on the structure, flow and oxygen levels of microvascular networks are needed, together with theoretical methods to integrate this information and predict physiologically relevant properties that are not directly measurable. Recent progress in optical imaging technologies for high-resolution in vivo measurement of the cerebral microvascular architecture, blood flow, and oxygenation enables construction of detailed computational models of cerebral hemodynamics and oxygen transport based on realistic three-dimensional microvascular networks. In this article, we review state-of-the-art optical microscopy technologies for quantitative in vivo imaging of cerebral microvascular structure, blood flow and oxygenation, and theoretical methods that utilize such data to generate spatially resolved models for blood flow and oxygen transport. These “bottom-up” models are essential for the understanding of the processes governing brain oxygenation in normal and disease states and for eventual translation of the lessons learned from animal studies to humans.Publication Large arteriolar component of oxygen delivery implies safe margin of oxygen supply to cerebral tissue(2014) Sakadzic, Sava; Mandeville, Emiri; Gagnon, Louis; Musacchia, Joseph J.; Yaseen, Mohammad; Yücel, Meryem A.; Lefebvre, Joel; Lesage, Frédéric; Dale, Anders M.; Eikermann-Haerter, Katharina; Ayata, Cenk; Srinivasan, Vivek J.; Lo, Eng; Devor, Anna; Boas, DavidWhat is the organization of cerebral microvascular oxygenation and morphology that allows adequate tissue oxygenation at different activity levels? We address this question in the mouse cerebral cortex using microscopic imaging of intravascular O2 partial pressure and blood flow combined with numerical modeling. Here we show that parenchymal arterioles are responsible for 50% of the extracted O2 at baseline activity and the majority of the remaining O2 exchange takes place within the first few capillary branches. Most capillaries release little O2 at baseline acting as an O2 reserve that is recruited during increased neuronal activity or decreased blood flow. Our results challenge the common perception that capillaries are the major site of O2 delivery to cerebral tissue. The understanding of oxygenation distribution along arterio-capillary paths may have profound implications for the interpretation of BOLD fMRI signal and for evaluating microvascular O2 delivery capacity to support cerebral tissue in disease.Publication Phasor analysis of NADH FLIM identifies pharmacological disruptions to mitochondrial metabolic processes in the rodent cerebral cortex(Public Library of Science, 2018) Gómez, Carlos A.; Sutin, Jason; Wu, Weicheng; Fu, Buyin; Uhlirova, Hana; Devor, Anna; Boas, David; Sakadzic, Sava; Yaseen, MohammadInvestigating cerebral metabolism in vivo at a microscopic level is essential for understanding brain function and its pathological alterations. The intricate signaling and metabolic dynamics between neurons, glia, and microvasculature requires much more detailed understanding to better comprehend the mechanisms governing brain function and its disease-related changes. We recently demonstrated that pharmacologically-induced alterations to different steps of cerebral metabolism can be distinguished utilizing 2-photon fluorescence lifetime imaging of endogenous reduced nicotinamide adenine dinucleotide (NADH) fluorescence in vivo. Here, we evaluate the ability of the phasor analysis method to identify these pharmacological metabolic alterations and compare the method’s performance with more conventional nonlinear curve-fitting analysis. Visualization of phasor data, both at the fundamental laser repetition frequency and its second harmonic, enables resolution of pharmacologically-induced alterations to mitochondrial metabolic processes from baseline cerebral metabolism. Compared to our previous classification models based on nonlinear curve-fitting, phasor–based models required fewer parameters and yielded comparable or improved classification accuracy. Fluorescence lifetime imaging of NADH and phasor analysis shows utility for detecting metabolic alterations and will lead to a deeper understanding of cerebral energetics and its pathological changes.