Name: neurovascular network explorer 2.0: a simple tool for exploring and sharing a database of optogenetically-evoked vasomotion in mouse cortex in vivo
Uploaded: 2018-05-04T13:00:00
Description: Watch this Scientific Journal Video about Neurovascular Network Explorer 2.0: A Simple Tool for Exploring and Sharing a Database of Optogenetically-evoked Vasomotion in Mouse Cortex In Vivo at JoVE.co

We gratefully acknowledge support from the NIH (NS057198, EB00790, MH111359, and S10RR029050) and the Ministry of Education, Youth and Sports of the Czech Republic (CEITEC 2020, LQ1601). KK was supported by postdoctoral fellowships from the International Headache Society in 2014 and The Scientific and Technological Research Council of Turkey in 2015. MT was supported by postdoctoral fellowship from the German Research Foundation (DFG TH 2031/1).

1. Installation of NNE 2.0
<ol>
	<li>Go to UCSD Neurovascular Imaging Laboratory website1 and left-click at &#8216;NNE 2.0 HDbase v1.0&#8217; to download the zipped program files to the desired location on your PC. 
	NOTE: NNE 2.0 requires a Windows-operating system of versions 7-10, at least 2.8 GB of free space to download the zipped file and 6.9 GB to install the program.</li>
	<li>Unzip &#8216;NNE2_HDbase_v1.0.zip&#8217;. 
	NOTE: The unzipped folder NNE2 contains 10 files: &#8216;h...

<ol>
	<li>. Use Our Data Available from: <a target="_blank" href="https://neurosciences.ucsd.edu/research/labs/nil/Pages/UseOurData.aspx">https://neurosciences.ucsd.edu/research/labs/nil/Pages/UseOurData.aspx</a> (2017)</li><li>Craddock, R. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Imaging+human+connectomes+at+the+macroscale.">Imaging human connectomes at the macroscale.</a> Nat Methods. 10 (6), 524-539 (2013).</li><li>Devor, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Frontiers+in+optical+imaging+of+cerebral+blood+flow+and+metabolism.">Frontiers in optical imaging of cerebral blood flow and metabolism.</a> J Cereb Blood Flow Metab. 32 (7), 1259-1276 (2012).</li><li>Ji, N., Freeman, J., Smith, S. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Technologies+for+imaging+neural+activity+in+large+volumes.">Technologies for imaging neural activity in large volumes.</a> Nat Neurosci. 19 (9), 1154-1164 (2016).</li><li>Maze, I., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Analytical+tools+and+current+challenges+in+the+modern+era+of+neuroepigenomics.">Analytical tools and current challenges in the modern era of neuroepigenomics.</a> Nat Neurosci. 17 (11), 1476-1490 (2014).</li><li>Medland, S. E., Jahanshad, N., Neale, B. M., Thompson, P. 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J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Progress+and+challenges+in+probing+the+human+brain.">Progress and challenges in probing the human brain.</a> Nature. 526 (7573), 371-379 (2015).</li><li>Kotter, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neuroscience+databases:+tools+for+exploring+brain+structure-function+relationships.">Neuroscience databases: tools for exploring brain structure-function relationships.</a> Philos Trans R Soc Lond B Biol Sci. 356 (1412), 1111-1120 (2001).</li><li>Uhlirova, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+roadmap+for+estimation+of+cell-type-specific+neuronal+activity+from+non-invasive+measurements.">The roadmap for estimation of cell-type-specific neuronal activity from non-invasive measurements.</a> Philos Trans R Soc Lond B Biol Sci. 371 (1705), (2016).</li><li>Aine, C. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Multimodal+Neuroimaging+in+Schizophrenia:+Description+and+Dissemination.">Multimodal Neuroimaging in Schizophrenia: Description and Dissemination.</a> Neuroinformatics. , (2017).</li><li>Amunts, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=BigBrain:+an+ultrahigh-resolution+3D+human+brain+model.">BigBrain: an ultrahigh-resolution 3D human brain model.</a> Science. 340 (6139), 1472-1475 (2013).</li><li>Laird, A. R., Lancaster, J. L., Fox, P. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=BrainMap:+the+social+evolution+of+a+human+brain+mapping+database.">BrainMap: the social evolution of a human brain mapping database.</a> Neuroinformatics. 3 (1), 65-78 (2005).</li><li>Lein, E. S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Genome-wide+atlas+of+gene+expression+in+the+adult+mouse+brain.">Genome-wide atlas of gene expression in the adult mouse brain.</a> Nature. 445 (7124), 168-176 (2007).</li><li>Shin, D. D., Ozyurt, I. B., Liu, T. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Cerebral+Blood+Flow+Biomedical+Informatics+Research+Network+(CBFBIRN)+database+and+analysis+pipeline+for+arterial+spin+labeling+MRI+data.">The Cerebral Blood Flow Biomedical Informatics Research Network (CBFBIRN) database and analysis pipeline for arterial spin labeling MRI data.</a> Front Neuroinform. 7, 21 (2013).</li><li>Uhlirova, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neurovascular+Network+Explorer+2.0:+A+Database+of+2-Photon+Single-Vessel+Diameter+Measurements+from+Mouse+SI+Cortex+in+Response+To+Optogenetic+Stimulation.">Neurovascular Network Explorer 2.0: A Database of 2-Photon Single-Vessel Diameter Measurements from Mouse SI Cortex in Response To Optogenetic Stimulation.</a> Front Neuroinform. 11, 4 (2017).</li><li>Sridhar, V. B., Tian, P., Dale, A. M., Devor, A., Saisan, P. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neurovascular+Network+Explorer+1.0:+a+database+of+2-photon+single-vessel+diameter+measurements+with+MATLAB((R))+graphical+user+interface.">Neurovascular Network Explorer 1.0: a database of 2-photon single-vessel diameter measurements with MATLAB((R)) graphical user interface.</a> Front Neuroinform. 8, 56 (2014).</li><li>Tian, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cortical+depth-specific+microvascular+dilation+underlies+laminar+differences+in+blood+oxygenation+level-dependent+functional+MRI+signal.">Cortical depth-specific microvascular dilation underlies laminar differences in blood oxygenation level-dependent functional MRI signal.</a> Proc Natl Acad Sci U S A. 107 (34), 15246-15251 (2010).</li><li>. Use Our Data Available from: <a target="_blank" href="https://neurosciences.ucsd.edu/research/labs/nil/Pages/UseOurData.aspx">https://neurosciences.ucsd.edu/research/labs/nil/Pages/UseOurData.aspx</a> (2017)</li><li>Uhlirova, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cell+type+specificity+of+neurovascular+coupling+in+cerebral+cortex.">Cell type specificity of neurovascular coupling in cerebral cortex.</a> Elife. 5, (2016).</li><li>Gagnon, L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Quantifying+the+microvascular+origin+of+BOLD-fMRI+from+first+principles+with+two-photon+microscopy+and+an+oxygen-sensitive+nanoprobe.">Quantifying the microvascular origin of BOLD-fMRI from first principles with two-photon microscopy and an oxygen-sensitive nanoprobe.</a> J Neurosci. 35 (8), 3663-3675 (2015).</li><li>Sakadzic, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Two-photon+high-resolution+measurement+of+partial+pressure+of+oxygen+in+cerebral+vasculature+and+tissue.">Two-photon high-resolution measurement of partial pressure of oxygen in cerebral vasculature and tissue.</a> Nat Methods. 7 (9), 755-759 (2010).</li><li>Nizar, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=In+vivo+stimulus-induced+vasodilation+occurs+without+IP3+receptor+activation+and+may+precede+astrocytic+calcium+increase.">In vivo stimulus-induced vasodilation occurs without IP3 receptor activation and may precede astrocytic calcium increase.</a> J Neurosci. 33 (19), 8411-8422 (2013).</li><li>Reznichenko, L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=In+vivo+alterations+in+calcium+buffering+capacity+in+transgenic+mouse+model+of+synucleinopathy.">In vivo alterations in calcium buffering capacity in transgenic mouse model of synucleinopathy.</a> J Neurosci. 32 (29), 9992-9998 (2012).</li><li>Langer, J., Rose, C. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Synaptically+induced+sodium+signals+in+hippocampal+astrocytes+in+situ.">Synaptically induced sodium signals in hippocampal astrocytes in situ.</a> J Physiol. 587 (Pt 24), 5859-5877 (2009).</li><li>Gong, Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=High-speed+recording+of+neural+spikes+in+awake+mice+and+flies+with+a+fluorescent+voltage+sensor.">High-speed recording of neural spikes in awake mice and flies with a fluorescent voltage sensor.</a> Science. 350 (6266), 1361-1366 (2015).</li><li>Tantama, M., Hung, Y. 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K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+effect+of+a+serotonin-induced+dissociation+between+spiking+and+perisynaptic+activity+on+BOLD+functional+MRI.">The effect of a serotonin-induced dissociation between spiking and perisynaptic activity on BOLD functional MRI.</a> Proc Natl Acad Sci U S A. 105 (18), 6759-6764 (2008).</li><li>Lemmon, V. P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Minimum+information+about+a+spinal+cord+injury+experiment:+a+proposed+reporting+standard+for+spinal+cord+injury+experiments.">Minimum information about a spinal cord injury experiment: a proposed reporting standard for spinal cord injury experiments.</a> J Neurotrauma. 31 (15), 1354-1361 (2014).</li><li>Ascoli, G. A., Donohue, D. 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NNE 2.0 was written in order to share the vascular imaging data of a specific study20 but with the intention of developing a simple tool for sharing and exploring data of similar kind by other users. Researchers interested in inspecting the associated database of vascular data may use the GUI to browse the data, select subsets of data, compare them to their own experimental results or process them further using their own computational procedures. Users familiar with MATLAB can utilize directly the...

The brain is considered one of the most intricate organs and the desire to untangle its complex function is unflagging. It is being studied at different scales from the molecular to the behavioral level using a wide palette of tools2,3,4,5,6,7,8. The amount of non-homogeneous experimental data grows with unprecedented speed. The awareness of the need for experimental data sharing, organization and standardization grows with the amount of acquired data. It has become evident that neuroinformatics will play a critical role in integrating experimental data across scales into models of brain function and dysfunction9,10.
To this end some studies, especially larger-scale studies, were able to earmark resources to make their results available via extensive databases11,12,13,14,15. However, a vast amount of experimental data from individual studies and regular-sized laboratories never reached the wider research community. This is mainly for two reasons: first, more dedicated time is needed to build a database and create tools that would enable the user to interact with the database; and second, more money is needed to support these tasks. Motivated by these challenges, a MATLAB based graphical user interface (GUI) engine called the Neurovascular Network Explorer 2.0 (NNE 2.0)16 was developed as a simple and low-cost tool for databasing, sharing and exploring of vascular imaging data. This manuscript provides a manual for operation of NNE 2.0 and the associated database of experimental data.
NNE 2.0 is already a second-generation software engine. The first generation, called Neurovascular Network Explorer 1.0 (NNE 1.0)17 was built to interact with a database of sensory-evoked vasodilation in rat primary somatosensory cortex (SI) in vivo measured by 2-photon microscopy18. NNE 1.0, its source code as well as the associated database are freely downloadable as a zipped file called &#8216;NNE 1 Tian&#8217; from UCSD Neurovascular Imaging Laboratory website1. More information about NNE 1.0 and the associated database can be found in17.
The second generation, the NNE 2.0, interacts with a database of optogenetically-evoked dilation of individual vessels in mice SI in vivo measured by 2-photon microscopy20. The user can browse, select and visualize data based on selection categories such as cortical depth, branching order, vessel diameter, animal subject or a particular arteriolar tree. The GUI further performs simple mathematical operations such as averaging and peak-normalization in selected categories. NNE 2.0 enables to view and browse through images capturing 3D volumes of vasculature as well as identify the location of the functional measurement within the vascular trees. This feature can be used to reconstruct vascular morphologies in 3D and populate them with real single-vessel vaso-motion measurements. These reconstructions can in turn be incorporated into computational models of brain function21,22. NNE 2.0, its source code and the associated database are freely downloadable as a zipped file called &#8216;NNE 2.0 HDbase v1.0&#8217; from UCSD Neurovascular Imaging Laboratory website1.
NNE 2.0 works with a database called &#39;vdb.mat&#39;. This database is a matrix containing temporal profiles (time-courses) of single vessel diameter changes evoked by an optogenetic stimulus and measured at different locations of arteriolar trees. Each time-course was computed using custom-written software. It calculates the relative change of a vessel diameter from expansion of a fluorescent intensity profile acquired by scanning across the vessel. The fluorescent contrast was presented by intravascular injection of fluorescein isothiocyanate (FITC)-labeled dextran. For more information about the data and analysis procedures, please see20,23. The database has 305 time-courses (i.e. database entries) in total. In addition to the diameter change, each entry to the database holds an array of additional metadata which (1) quantify the time-course (2) describe the measured vessel and (3) identify the measurement location within a 3D volume of cortical vasculature. The metadata include the onset time, peak amplitude, peak amplitude time, cortical depth, branching order, vessel diameter at baseline, path to original reference images and 3D image stacks for each measurement and low-magnification maps of brain surface vasculature. Please see all parameters in the metadata listed and described in detail previously in Table 116.
NNE 2.0 interacts with reference images that are X-Y scans of a plane where the diameter measurement occurred. Each database entry has one corresponding reference image with a reference name displayed in the GUI. Each database entry also has an associated stack of images (3D stack) capturing a 3D volume of the vascular tree within which the measurement occurred. The GUI enables to choose a particular database entry and display the corresponding reference image as well as the 3D stack. It also guides the user to find the matching reference image and frame in the 3D stack (the same features can be found in both images). All stack and reference images in their full resolution (1024 pix x 1024 pix) are included in folders hana_stk and hana_refs, respectively. Low-magnification maps of brain vasculature are included in folder &#39;maps&#39;. All three folders as well as the database matrix &#8216;vdb.mat&#8217; are downloaded in the zipped file &#8216;NNE 2.0 HDbase v1.0&#8217; from the UCSD Neurovascular Imaging Laboratory website1 and saved to the root folder of NNE 2.0 during the installation process.
The GUI has been designed as a set of four panels (Panel 1 (Main Panel) &#8211; Panel 4) which open sequentially as the user explores the database and selects specific data based on selection categories. Each panel is divided into two main parts: (1) the right column provides the possibility to interact with the database by selecting parameters and categories of the data and displays important information from the metadata; (2) the left column displays the data in the form of time-courses (diameter change in time) and scatter-plots. There are four types of scatter plots displaying (1) dilation onset time (2) time of the dilation peak (3) maximum diameter change (peak amplitude) and (4) baseline diameter (diameter before stimulation) as function of cortical depth. The user has the possibility to display average time-courses and values for selected data grouped either by cortical depth or branching order. This is to highlight the feature of gradient diameter-change behavior with increasing depth and branching order20. NNE 2.0 allows the user to export the selected subset of data in the format of &#39;.xls&#39;, &#39;.csv&#39; or &#39;.mat&#39;.

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	<tbody>
		<tr height="40">
			<td height="40" style="height:40px;width:216px;">MATLAB</td>
			<td style="width:123px;">MathWorks</td>
			<td style="width:344px;"></td>
			<td style="width:167px;">program</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">Winrar</td>
			<td>Rarlabs</td>
			<td></td>
			<td>program</td>
		</tr>
	</tbody>
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neurovascular network explorer 2.0: a simple tool for exploring and sharing a database of optogenetically-evoked vasomotion in mouse cortex in vivo

The importance of sharing experimental data in neuroscience grows with the amount and complexity of data acquired and various techniques used to obtain and process these data. However, the majority of experimental data, especially from individual studies of regular-sized laboratories never reach wider research community. A graphical user interface (GUI) engine called Neurovascular Network Explorer 2.0 (NNE 2.0) has been created as a tool for simple and low-cost sharing and exploring of vascular imaging data. NNE 2.0 interacts with a database containing optogenetically-evoked dilation/constriction time-courses of individual vessels measured in mice somatosensory cortex in vivo by 2-photon microscopy. NNE 2.0 enables selection and display of the time-courses based on different criteria (subject, branching order, cortical depth, vessel diameter, arteriolar tree) as well as simple mathematical manipulation (e.g. averaging, peak-normalization) and data export. It supports visualization of the vascular network in 3D and enables localization of the individual functional vessel diameter measurements within vascular trees.
NNE 2.0, its source code, and the corresponding database are freely downloadable from UCSD Neurovascular Imaging Laboratory website1. The source code can be utilized by the users to explore the associated database or as a template for databasing and sharing their own experimental results provided the appropriate format.

NNE 2.0 and the associate database serve to browse and view the data of the database, sort out the data based on selection criteria, download the selected data, and find the vascular measurements within the corresponding vascular tree.
Panel 1 features selection of data based on categories: &#39;Cortical Depth&#39;, &#39;Branching Order&#39;, &#39;Baseline Diameter&#39; and &#39;Subjects&#39; &#8211; Figure ...

Watch this Scientific Journal Video about Neurovascular Network Explorer 2.0: A Simple Tool for Exploring and Sharing a Database of Optogenetically-evoked Vasomotion in Mouse Cortex In Vivo at JoVE.co

Neurovascular Network Explorer 2.0: A Simple Tool for Exploring and Sharing a Database of Optogenetically-evoked Vasomotion in Mouse Cortex In Vivo

A graphical user interface for exploring and sharing a database of optogenetically-induced vascular responses in mouse somatosensory cortex in vivo measured by 2-photon microscopy is presented. It allows browsing the data, criteria-based selection, averaging, localization of measurements within a 3D volume of vasculature and exporting the data.

The importance of sharing experimental data in neuroscience grows with the amount and complexity of data acquired and various techniques used to obtain ...

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