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Neuroimage. 2014 Dec;103:171-180. doi: 10.1016/j.neuroimage.2014.09.023. Epub 2014 Sep 16.

SPECT-imaging of activity-dependent changes in regional cerebral blood flow induced by electrical and optogenetic self-stimulation in mice.

Author information

1
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.
2
Leibniz-Institute for Neurobiology, Brenneckestr. 6, D-39118 Magdeburg, Germany. Electronic address: mlippert@lin-magdeburg.de.
3
Deutsches Zentrum für neurodegenerative Erkrankungen (DZNE), Leipziger Strasse 44, D-39120 Magdeburg, Germany. Electronic address: frank.angenstein@dzne.de.
4
Leibniz-Institute for Neurobiology, Brenneckestr. 6, D-39118 Magdeburg, Germany. Electronic address: jenni.neubert@charite.de.
5
Department of Radiology and Nuclear Medicine, University Hospital Magdeburg, Leipziger Strasse 44, D-39120 Magdeburg, Germany. Electronic address: annette.pethe@med.ovgu.de.
6
Department of Radiology and Nuclear Medicine, University Hospital Magdeburg, Leipziger Strasse 44, D-39120 Magdeburg, Germany. Electronic address: oliver.grosser@med.ovgu.de.
7
Department of Radiology and Nuclear Medicine, University Hospital Magdeburg, Leipziger Strasse 44, D-39120 Magdeburg, Germany. Electronic address: holger.amthauer@med.ovgu.de.
8
Leibniz-Institute for Neurobiology, Brenneckestr. 6, D-39118 Magdeburg, Germany. Electronic address: ulrich.schroeder@lin-magdeburg.de.
9
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.
10
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.
11
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.
12
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.

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.

KEYWORDS:

PET; SPECT; fMRI; mouse; optogenetics; reward

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