title: SPECT-imaging of activity-dependent changes in regional cerebral blood flow induced by electrical and optogenetic self-stimulation in mice.
abstract: Electrical and optogenetic methods for brain stimulation are widely used in rodents for manipulating behavior and analyzing functional connectivities in neuronal circuits. High-resolution in vivo imaging of the global, brain-wide, activation patterns induced by these stimulations has remained challenging, in particular in awake behaving mice. We here mapped brain activation patterns in awake, intracranially self-stimulating mice using a novel protocol for single-photon emission computed tomography (SPECT) imaging of regional cerebral blood flow (rCBF). Mice were implanted with either electrodes for electrical stimulation of the medial forebrain bundle (mfb-microstim) or with optical fibers for blue-light stimulation of channelrhodopsin-2 expressing neurons in the ventral tegmental area (vta-optostim). After training for self-stimulation by current or light application, respectively, mice were implanted with jugular vein catheters and intravenously injected with the flow tracer 99m-technetium hexamethylpropyleneamine oxime (99mTc-HMPAO) during seven to ten minutes of intracranial self-stimulation or ongoing behavior without stimulation. The 99mTc-brain distributions were mapped in anesthetized animals after stimulation using multipinhole SPECT. Upon self-stimulation rCBF strongly increased at the electrode tip in mfb-microstim mice. In vta-optostim mice peak activations were found outside the stimulation site. Partly overlapping brain-wide networks of activations and deactivations were found in both groups. When testing all self-stimulating mice against all controls highly significant activations were found in the rostromedial nucleus accumbens shell. SPECT-imaging of rCBF using intravenous tracer-injection during ongoing behavior is a new tool for imaging regional brain activation patterns in awake behaving rodents providing higher spatial and temporal resolutions than 18F-2-fluoro-2-dexoyglucose positron emission tomography.
authors.affiliation: Leibniz-Institute for Neurobiology, Brenneckestr. 6, D-39118 Magdeburg, Germany; Otto von Guericke University Magdeburg, Institute of Biology, Leipziger Strasse 44, D-39120 Magdeburg, Germany. Electronic address: angela.kolodziej@lin-magdeburg.de.
authors.forename: Angela
authors.initials: A
authors.lastname: Kolodziej
authors.affiliation: Leibniz-Institute for Neurobiology, Brenneckestr. 6, D-39118 Magdeburg, Germany. Electronic address: mlippert@lin-magdeburg.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Lippert
authors.affiliation: Deutsches Zentrum für neurodegenerative Erkrankungen (DZNE), Leipziger Strasse 44, D-39120 Magdeburg, Germany. Electronic address: frank.angenstein@dzne.de.
authors.forename: Frank
authors.initials: F
authors.lastname: Angenstein
authors.affiliation: Leibniz-Institute for Neurobiology, Brenneckestr. 6, D-39118 Magdeburg, Germany. Electronic address: jenni.neubert@charite.de.
authors.forename: Jenni
authors.initials: J
authors.lastname: Neubert
authors.affiliation: Department of Radiology and Nuclear Medicine, University Hospital Magdeburg, Leipziger Strasse 44, D-39120 Magdeburg, Germany. Electronic address: annette.pethe@med.ovgu.de.
authors.forename: Annette
authors.initials: A
authors.lastname: Pethe
authors.affiliation: Department of Radiology and Nuclear Medicine, University Hospital Magdeburg, Leipziger Strasse 44, D-39120 Magdeburg, Germany. Electronic address: oliver.grosser@med.ovgu.de.
authors.forename: Oliver S
authors.initials: OS
authors.lastname: Grosser
authors.affiliation: Department of Radiology and Nuclear Medicine, University Hospital Magdeburg, Leipziger Strasse 44, D-39120 Magdeburg, Germany. Electronic address: holger.amthauer@med.ovgu.de.
authors.forename: Holger
authors.initials: H
authors.lastname: Amthauer
authors.affiliation: Leibniz-Institute for Neurobiology, Brenneckestr. 6, D-39118 Magdeburg, Germany. Electronic address: ulrich.schroeder@lin-magdeburg.de.
authors.forename: Ulrich H
authors.initials: UH
authors.lastname: Schroeder
authors.affiliation: Leibniz-Institute for Neurobiology, Brenneckestr. 6, D-39118 Magdeburg, Germany; Deutsches Zentrum für neurodegenerative Erkrankungen (DZNE), Leipziger Strasse 44, D-39120 Magdeburg, Germany. Electronic address: reymann@lin-magdeburg.de.
authors.forename: Klaus G
authors.initials: KG
authors.lastname: Reymann
authors.affiliation: Leibniz-Institute for Neurobiology, Brenneckestr. 6, D-39118 Magdeburg, Germany; Center for Behavioral Brain Sciences (CBBS), Otto-von-Guericke-University Magdeburg, Universitätsplatz 2, D-39106 Magdeburg, Germany. Electronic address: henning.scheich@lin-magdeburg.de.
authors.forename: Henning
authors.initials: H
authors.lastname: Scheich
authors.affiliation: Leibniz-Institute for Neurobiology, Brenneckestr. 6, D-39118 Magdeburg, Germany; Otto von Guericke University Magdeburg, Institute of Biology, Leipziger Strasse 44, D-39120 Magdeburg, Germany; Center for Behavioral Brain Sciences (CBBS), Otto-von-Guericke-University Magdeburg, Universitätsplatz 2, D-39106 Magdeburg, Germany. Electronic address: frank.ohl@lin-magdeburg.de.
authors.forename: Frank W
authors.initials: FW
authors.lastname: Ohl
authors.affiliation: Leibniz-Institute for Neurobiology, Brenneckestr. 6, D-39118 Magdeburg, Germany; Otto-von-Guericke University Magdeburg, Department of Neurology, Leipziger Str. 44, D-39120 Magdeburg, Germany. Electronic address: juergen.goldschmidt@lin-magdeburg.de.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Goldschmidt
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging*; D001931:Brain Mapping / Q000379:methods*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D062308:Optogenetics / Q000379:methods*; D019275:Radiopharmaceuticals; D012201:Reward; D012653:Self Stimulation; D019690:Technetium Tc 99m Exametazime; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
chemical_list: D019275:Radiopharmaceuticals; D019690:Technetium Tc 99m Exametazime
keywords: PET; SPECT; fMRI; mouse; optogenetics; reward